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Active Surveillance for Cancer Doesn’t Increase Malpractice Risk
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
It Takes a Village: Treating Patients for NSCLC Brain Metastases
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
FROM ELCC 2024
Women’s Cancers: Clinicians Research, Advise on Sexual Dysfunction
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
FROM SGO 2024
Debate: Does ctDNA Have Role in Monitoring Tx Efficacy in Lung Cancer?
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
FROM ELCC 2024
Diarrhea in Cancer Therapies — Part 1: Chemotherapeutics
Patients with cancer receiving chemotherapeutics may develop diarrhea, which can be highly distressing. In a recent journal article, oncologist Marcus Hentrich, MD, and gastroenterologist Volker Penndorf, MD, PhD, both of Rotkreuzklinikum in Munich, Germany, explained how affected patients should be treated.
As Dr. Hentrich and Dr. Penndorf explained, classical According to the authors, the risk for toxic mucosal damage (toxic enteritis) increases with the severity and duration of neutropenia. Up to two thirds of patients with neutropenia develop diarrhea, and an infectious cause is rarely identified.
The cytostatic drug irinotecan, which can lead to an acute cholinergic syndrome within 24 hours, is a special case. This syndrome is characterized by watery diarrhea, abdominal cramps, vomiting, sweating, and bradycardia. Additionally, the development of late-onset diarrhea, occurring approximately 3 days after administration, is frequent.
According to the authors, risk factors for toxic enteritis with diarrhea include advanced age, poor performance and nutritional status, simultaneous radiotherapy of the abdomen and pelvis, and preexisting intestinal conditions.
Medication prophylaxis for chemotherapy-induced diarrhea has not been established. An exception is atropine for prophylaxis and treatment of irinotecan-induced cholinergic syndrome.
Indications for diagnostic procedures are outlined in the current German guideline for supportive therapy in patients with cancer.
For diarrhea accompanied by fever, blood cultures are mandatory. A complete blood count provides information on various aspects (leukocytosis as an inflammatory reaction, neutropenia as a marker for infection risk, hemoglobin as a marker for possible hemoconcentration or existing bleeding, and thrombocytopenia as a marker for bleeding tendency). Disproportionate thrombocytopenia may warrant assessment of fragmented cells and enterohemorrhagic Escherichia coli diagnostics.
To assess electrolyte and fluid loss, electrolytes, albumin, and total protein should be measured. The C-reactive protein value may help identify inflammatory conditions. It may also be elevated, however, because of tumor-related factors. Measuring urea and creatinine allows for estimating whether there is already a prerenal impairment of kidney function. Liver function parameters are mandatory for critically ill patients. In patients with hypotension or tachycardia, blood gas analysis and lactate determination are advisable. Among imaging techniques, ultrasound may be helpful. Indications for conventional abdominal x-ray are rare. In the presence of clinical signs of peritoneal irritation (such as guarding and rebound tenderness), a CT scan should be considered to detect further complications (perforation, ileus, enterocolitis, etc.) promptly.
Endoscopic examinations are recommended only in cases of persistent, worsening symptoms, according to the guideline. Colonoscopy is contraindicated in suspected neutropenic enterocolitis (NEC) because of the risk for perforation.
According to Dr. Hentrich and Dr. Penndorf, diarrhea therapy is carried out in stages and depends on the severity and response to each therapy. The Common Terminology Criteria for Adverse Events distinguishes the following severity grades:
- Grade 1: < four stools per day above baseline
- Grade 2: Four to six stools per day above baseline
- Grade 3: ≥ seven stools per day above baseline; fecal incontinence, hospitalization indicated; limited activities of daily living
- Grade 4: Life-threatening consequences, urgent intervention indicated
Therapy for Grades 1-2
The standard therapeutic after excluding infectious causes is loperamide (initially 4 mg orally, followed by 2 mg every 2-4 hours). A daily dose should not exceed 16 mg.
For irinotecan-associated diarrhea, adjunctive administration of budesonide (3 mg orally three times per day) with loperamide was shown to be effective in a small, randomized study (off-label). Another randomized study demonstrated the efficacy of combining loperamide with racecadotril (100 mg orally three times per day for 48 hours).
Therapy for Grade 3 Diarrhea
In severe diarrhea persisting despite loperamide therapy for 24-48 hours, octreotide (100-150 μg subcutaneously three times per day) may be administered (maximum three times 500 μg). Although octreotide is often used successfully for chemotherapy-induced diarrhea, it is not approved for this indication (off-label use).
According to the authors, other therapy options for loperamide-refractory diarrhea include codeine, tincture of opium, budesonide, and racecadotril. Psyllium husk or diphenoxylate plus atropine may also be attempted. In patients with prolonged neutropenia, overdosing of motility inhibitors should be avoided because of the risk for ileus.
The use of probiotics for chemotherapy-induced diarrhea cannot be generally recommended because of insufficient evidence, and cases of probiotic-associated bacteremia and fungemia have been described.
A particularly serious complication of intensive chemotherapy associated with diarrhea is NEC. It is characterized by fever, abdominal pain, and diarrhea during severe neutropenia (neutrophil count < 500/μL), the authors explained. NEC occurs predominantly, but not exclusively, after intensive chemotherapy for hematologic malignancies, especially acute leukemias.
More common than NEC and often preceding it is the so-called chemotherapy-associated bowel syndrome. It is characterized by fever ≥ 37.8 °C and abdominal pain or absence of stool for at least 72 hours.
Therapy consists of conservative symptomatic measures such as diet, adequate hydration with electrolyte balance, and analgesia. Due to the high risk for bacteremia, antibiotic therapy is indicated after blood cultures are obtained (piperacillin-tazobactam or a carbapenem). According to the authors, NEC improves in most patients with neutrophil regeneration. Granulocyte colony-stimulating factor therapy appears reasonable in this context, although conclusive studies are lacking. Surgical intervention with removal of necrotic bowel segments may be considered in exceptional cases.
This story was translated from Univadis Germany, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Patients with cancer receiving chemotherapeutics may develop diarrhea, which can be highly distressing. In a recent journal article, oncologist Marcus Hentrich, MD, and gastroenterologist Volker Penndorf, MD, PhD, both of Rotkreuzklinikum in Munich, Germany, explained how affected patients should be treated.
As Dr. Hentrich and Dr. Penndorf explained, classical According to the authors, the risk for toxic mucosal damage (toxic enteritis) increases with the severity and duration of neutropenia. Up to two thirds of patients with neutropenia develop diarrhea, and an infectious cause is rarely identified.
The cytostatic drug irinotecan, which can lead to an acute cholinergic syndrome within 24 hours, is a special case. This syndrome is characterized by watery diarrhea, abdominal cramps, vomiting, sweating, and bradycardia. Additionally, the development of late-onset diarrhea, occurring approximately 3 days after administration, is frequent.
According to the authors, risk factors for toxic enteritis with diarrhea include advanced age, poor performance and nutritional status, simultaneous radiotherapy of the abdomen and pelvis, and preexisting intestinal conditions.
Medication prophylaxis for chemotherapy-induced diarrhea has not been established. An exception is atropine for prophylaxis and treatment of irinotecan-induced cholinergic syndrome.
Indications for diagnostic procedures are outlined in the current German guideline for supportive therapy in patients with cancer.
For diarrhea accompanied by fever, blood cultures are mandatory. A complete blood count provides information on various aspects (leukocytosis as an inflammatory reaction, neutropenia as a marker for infection risk, hemoglobin as a marker for possible hemoconcentration or existing bleeding, and thrombocytopenia as a marker for bleeding tendency). Disproportionate thrombocytopenia may warrant assessment of fragmented cells and enterohemorrhagic Escherichia coli diagnostics.
To assess electrolyte and fluid loss, electrolytes, albumin, and total protein should be measured. The C-reactive protein value may help identify inflammatory conditions. It may also be elevated, however, because of tumor-related factors. Measuring urea and creatinine allows for estimating whether there is already a prerenal impairment of kidney function. Liver function parameters are mandatory for critically ill patients. In patients with hypotension or tachycardia, blood gas analysis and lactate determination are advisable. Among imaging techniques, ultrasound may be helpful. Indications for conventional abdominal x-ray are rare. In the presence of clinical signs of peritoneal irritation (such as guarding and rebound tenderness), a CT scan should be considered to detect further complications (perforation, ileus, enterocolitis, etc.) promptly.
Endoscopic examinations are recommended only in cases of persistent, worsening symptoms, according to the guideline. Colonoscopy is contraindicated in suspected neutropenic enterocolitis (NEC) because of the risk for perforation.
According to Dr. Hentrich and Dr. Penndorf, diarrhea therapy is carried out in stages and depends on the severity and response to each therapy. The Common Terminology Criteria for Adverse Events distinguishes the following severity grades:
- Grade 1: < four stools per day above baseline
- Grade 2: Four to six stools per day above baseline
- Grade 3: ≥ seven stools per day above baseline; fecal incontinence, hospitalization indicated; limited activities of daily living
- Grade 4: Life-threatening consequences, urgent intervention indicated
Therapy for Grades 1-2
The standard therapeutic after excluding infectious causes is loperamide (initially 4 mg orally, followed by 2 mg every 2-4 hours). A daily dose should not exceed 16 mg.
For irinotecan-associated diarrhea, adjunctive administration of budesonide (3 mg orally three times per day) with loperamide was shown to be effective in a small, randomized study (off-label). Another randomized study demonstrated the efficacy of combining loperamide with racecadotril (100 mg orally three times per day for 48 hours).
Therapy for Grade 3 Diarrhea
In severe diarrhea persisting despite loperamide therapy for 24-48 hours, octreotide (100-150 μg subcutaneously three times per day) may be administered (maximum three times 500 μg). Although octreotide is often used successfully for chemotherapy-induced diarrhea, it is not approved for this indication (off-label use).
According to the authors, other therapy options for loperamide-refractory diarrhea include codeine, tincture of opium, budesonide, and racecadotril. Psyllium husk or diphenoxylate plus atropine may also be attempted. In patients with prolonged neutropenia, overdosing of motility inhibitors should be avoided because of the risk for ileus.
The use of probiotics for chemotherapy-induced diarrhea cannot be generally recommended because of insufficient evidence, and cases of probiotic-associated bacteremia and fungemia have been described.
A particularly serious complication of intensive chemotherapy associated with diarrhea is NEC. It is characterized by fever, abdominal pain, and diarrhea during severe neutropenia (neutrophil count < 500/μL), the authors explained. NEC occurs predominantly, but not exclusively, after intensive chemotherapy for hematologic malignancies, especially acute leukemias.
More common than NEC and often preceding it is the so-called chemotherapy-associated bowel syndrome. It is characterized by fever ≥ 37.8 °C and abdominal pain or absence of stool for at least 72 hours.
Therapy consists of conservative symptomatic measures such as diet, adequate hydration with electrolyte balance, and analgesia. Due to the high risk for bacteremia, antibiotic therapy is indicated after blood cultures are obtained (piperacillin-tazobactam or a carbapenem). According to the authors, NEC improves in most patients with neutrophil regeneration. Granulocyte colony-stimulating factor therapy appears reasonable in this context, although conclusive studies are lacking. Surgical intervention with removal of necrotic bowel segments may be considered in exceptional cases.
This story was translated from Univadis Germany, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Patients with cancer receiving chemotherapeutics may develop diarrhea, which can be highly distressing. In a recent journal article, oncologist Marcus Hentrich, MD, and gastroenterologist Volker Penndorf, MD, PhD, both of Rotkreuzklinikum in Munich, Germany, explained how affected patients should be treated.
As Dr. Hentrich and Dr. Penndorf explained, classical According to the authors, the risk for toxic mucosal damage (toxic enteritis) increases with the severity and duration of neutropenia. Up to two thirds of patients with neutropenia develop diarrhea, and an infectious cause is rarely identified.
The cytostatic drug irinotecan, which can lead to an acute cholinergic syndrome within 24 hours, is a special case. This syndrome is characterized by watery diarrhea, abdominal cramps, vomiting, sweating, and bradycardia. Additionally, the development of late-onset diarrhea, occurring approximately 3 days after administration, is frequent.
According to the authors, risk factors for toxic enteritis with diarrhea include advanced age, poor performance and nutritional status, simultaneous radiotherapy of the abdomen and pelvis, and preexisting intestinal conditions.
Medication prophylaxis for chemotherapy-induced diarrhea has not been established. An exception is atropine for prophylaxis and treatment of irinotecan-induced cholinergic syndrome.
Indications for diagnostic procedures are outlined in the current German guideline for supportive therapy in patients with cancer.
For diarrhea accompanied by fever, blood cultures are mandatory. A complete blood count provides information on various aspects (leukocytosis as an inflammatory reaction, neutropenia as a marker for infection risk, hemoglobin as a marker for possible hemoconcentration or existing bleeding, and thrombocytopenia as a marker for bleeding tendency). Disproportionate thrombocytopenia may warrant assessment of fragmented cells and enterohemorrhagic Escherichia coli diagnostics.
To assess electrolyte and fluid loss, electrolytes, albumin, and total protein should be measured. The C-reactive protein value may help identify inflammatory conditions. It may also be elevated, however, because of tumor-related factors. Measuring urea and creatinine allows for estimating whether there is already a prerenal impairment of kidney function. Liver function parameters are mandatory for critically ill patients. In patients with hypotension or tachycardia, blood gas analysis and lactate determination are advisable. Among imaging techniques, ultrasound may be helpful. Indications for conventional abdominal x-ray are rare. In the presence of clinical signs of peritoneal irritation (such as guarding and rebound tenderness), a CT scan should be considered to detect further complications (perforation, ileus, enterocolitis, etc.) promptly.
Endoscopic examinations are recommended only in cases of persistent, worsening symptoms, according to the guideline. Colonoscopy is contraindicated in suspected neutropenic enterocolitis (NEC) because of the risk for perforation.
According to Dr. Hentrich and Dr. Penndorf, diarrhea therapy is carried out in stages and depends on the severity and response to each therapy. The Common Terminology Criteria for Adverse Events distinguishes the following severity grades:
- Grade 1: < four stools per day above baseline
- Grade 2: Four to six stools per day above baseline
- Grade 3: ≥ seven stools per day above baseline; fecal incontinence, hospitalization indicated; limited activities of daily living
- Grade 4: Life-threatening consequences, urgent intervention indicated
Therapy for Grades 1-2
The standard therapeutic after excluding infectious causes is loperamide (initially 4 mg orally, followed by 2 mg every 2-4 hours). A daily dose should not exceed 16 mg.
For irinotecan-associated diarrhea, adjunctive administration of budesonide (3 mg orally three times per day) with loperamide was shown to be effective in a small, randomized study (off-label). Another randomized study demonstrated the efficacy of combining loperamide with racecadotril (100 mg orally three times per day for 48 hours).
Therapy for Grade 3 Diarrhea
In severe diarrhea persisting despite loperamide therapy for 24-48 hours, octreotide (100-150 μg subcutaneously three times per day) may be administered (maximum three times 500 μg). Although octreotide is often used successfully for chemotherapy-induced diarrhea, it is not approved for this indication (off-label use).
According to the authors, other therapy options for loperamide-refractory diarrhea include codeine, tincture of opium, budesonide, and racecadotril. Psyllium husk or diphenoxylate plus atropine may also be attempted. In patients with prolonged neutropenia, overdosing of motility inhibitors should be avoided because of the risk for ileus.
The use of probiotics for chemotherapy-induced diarrhea cannot be generally recommended because of insufficient evidence, and cases of probiotic-associated bacteremia and fungemia have been described.
A particularly serious complication of intensive chemotherapy associated with diarrhea is NEC. It is characterized by fever, abdominal pain, and diarrhea during severe neutropenia (neutrophil count < 500/μL), the authors explained. NEC occurs predominantly, but not exclusively, after intensive chemotherapy for hematologic malignancies, especially acute leukemias.
More common than NEC and often preceding it is the so-called chemotherapy-associated bowel syndrome. It is characterized by fever ≥ 37.8 °C and abdominal pain or absence of stool for at least 72 hours.
Therapy consists of conservative symptomatic measures such as diet, adequate hydration with electrolyte balance, and analgesia. Due to the high risk for bacteremia, antibiotic therapy is indicated after blood cultures are obtained (piperacillin-tazobactam or a carbapenem). According to the authors, NEC improves in most patients with neutrophil regeneration. Granulocyte colony-stimulating factor therapy appears reasonable in this context, although conclusive studies are lacking. Surgical intervention with removal of necrotic bowel segments may be considered in exceptional cases.
This story was translated from Univadis Germany, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Savolitinib Active Against MET Ex14 Mutated NSCLC
Savolitinib, a selective oral tyrosine kinase inhibitor, showed good activity against locally advanced or metastatic non–small cell lung cancer (NSCLC) bearing MET exon 14 mutations as both first-line therapy for treatment-naive patients and in second-line of therapy for previously treated patients
“The phase 3b study results further confirm savolitinib as a valuable targeted therapy option for naive and previously-treated non–small cell lung cancer with MET 14 exon mutations,” Yongchang Zhang, MD, said while presenting the final results of the trial at the European Lung Cancer Congress 2024.
For 87 previously untreated patients the objective response rate (ORR) as assessed by independent review, the primary endpoint, was 62.1%. For 79 patients receiving savolitinib in the second line, the ORR was 39.2%, reported Dr. Zhang, MD, of the Hunan Cancer Hospital in Changsha, China.
Preliminary results of this trial were reported at the World Conference on Lung Cancer in 2023.
Selective Inhibitor
Savolitinib (AZD6094, also called volitinib) is reported to be a highly selective oral inhibitor of the MET receptor tyrosine kinase (TKI). It is approved in China for the treatment of patients with NSCLC harboring MET exon 14 mutations that has progressed on prior systemic therapy, or patients who are unable to tolerate platinum-based chemotherapy.
In the phase 3b study, patients with MET ex14-positive tumors who were negative for EGFR, ALK or ROS1 alterations and were naive to a MET inhibitor were enrolled. Those who weighed 50 kg or greater received 600 mg savolitinib orally once daily for each 21-day cycle, while patients who weighed less than 50 kg received a 400-mg daily dose. Therapy continued until disease progression, death, or unacceptable toxicity.
Tumors were evaluated by investigators every 6 weeks for the first year, than every 12 weeks thereafter.
As noted before, ORR by independent review was 62.1% for treatment-naive patients and 39.2% for previously treated patients. The respective ORRs by investigator assessment were 59.8% and 43%. All responses in each arm were partial responses.
Median progression-free survival (PFS) after a median follow-up of 18 months for treatment-naive patients and 11 months for treatment-experienced patients was 13.7 months and 11 months, respectively.
Overall survival after a median follow-up of 20.8 months for treatment-naive patients and 12.5 months for previously treated patients was not reached in treatment-naive patients and not mature in treatment-experienced patients.
Grade 3 or greater treatment-emergent adverse events occurred in 74.1% of patients, including 3 events (1.8%) leading to death. Dose modifications were required for 74.7% of patients.
Grade 3 or greater adverse events included peripheral edema, liver enzyme elevations, abnormal liver function, decreased platelet and white blood cell counts, and vomiting.
Which TKI is Best?
Invited discussant Antonio Passaro, MD, PhD, from the European Institute of Oncology in Milan, noted that eligibility for treatment with savolitinib or other MET exon 14-targeting TKIs is limited to about 3% of patients with NSCLC of adenocarcinoma histology.
He said that savolitinib appears to be similar in performance to two other TKIs for NSCLC with MET exon-14 skipping mutations that are currently on the market in the United States, Europe, and Japan: capmatinib (Tabrecta) and tepotinib (Tepmetko).
“Globally, all the results show a numerically better performance when we use a selective TKI in first-line treatment over the second-line treatment, in particular for overall response rate,” he said.
Dr. Passaro noted that savolitinib differs from the other two MET TKIs in that PFS with savolitinib is similar for treatment-naive and previously treated patients.
He added, however, that “today it’s very difficult” to determine which is the “perfect” agent for a specific disease presentation, particularly since MET exon 14 skipping mutations can also be found in patients with squamous cell carcinomas and those with a history of smoking.
To get a better sense of which drug to use in a specific situation, it would be helpful to analyze trial results in the context of tumor histology, smoking history, programmed death protein 1-ligand 1 status, and co-mutations, he said.
The study was sponsored by Hutchmed. Dr. Zhang reported having no conflicts of interest. Dr. Passaro reported a consulting, advisory, or speakers bureau role for multiple companies, not including Hutchmed.
Savolitinib, a selective oral tyrosine kinase inhibitor, showed good activity against locally advanced or metastatic non–small cell lung cancer (NSCLC) bearing MET exon 14 mutations as both first-line therapy for treatment-naive patients and in second-line of therapy for previously treated patients
“The phase 3b study results further confirm savolitinib as a valuable targeted therapy option for naive and previously-treated non–small cell lung cancer with MET 14 exon mutations,” Yongchang Zhang, MD, said while presenting the final results of the trial at the European Lung Cancer Congress 2024.
For 87 previously untreated patients the objective response rate (ORR) as assessed by independent review, the primary endpoint, was 62.1%. For 79 patients receiving savolitinib in the second line, the ORR was 39.2%, reported Dr. Zhang, MD, of the Hunan Cancer Hospital in Changsha, China.
Preliminary results of this trial were reported at the World Conference on Lung Cancer in 2023.
Selective Inhibitor
Savolitinib (AZD6094, also called volitinib) is reported to be a highly selective oral inhibitor of the MET receptor tyrosine kinase (TKI). It is approved in China for the treatment of patients with NSCLC harboring MET exon 14 mutations that has progressed on prior systemic therapy, or patients who are unable to tolerate platinum-based chemotherapy.
In the phase 3b study, patients with MET ex14-positive tumors who were negative for EGFR, ALK or ROS1 alterations and were naive to a MET inhibitor were enrolled. Those who weighed 50 kg or greater received 600 mg savolitinib orally once daily for each 21-day cycle, while patients who weighed less than 50 kg received a 400-mg daily dose. Therapy continued until disease progression, death, or unacceptable toxicity.
Tumors were evaluated by investigators every 6 weeks for the first year, than every 12 weeks thereafter.
As noted before, ORR by independent review was 62.1% for treatment-naive patients and 39.2% for previously treated patients. The respective ORRs by investigator assessment were 59.8% and 43%. All responses in each arm were partial responses.
Median progression-free survival (PFS) after a median follow-up of 18 months for treatment-naive patients and 11 months for treatment-experienced patients was 13.7 months and 11 months, respectively.
Overall survival after a median follow-up of 20.8 months for treatment-naive patients and 12.5 months for previously treated patients was not reached in treatment-naive patients and not mature in treatment-experienced patients.
Grade 3 or greater treatment-emergent adverse events occurred in 74.1% of patients, including 3 events (1.8%) leading to death. Dose modifications were required for 74.7% of patients.
Grade 3 or greater adverse events included peripheral edema, liver enzyme elevations, abnormal liver function, decreased platelet and white blood cell counts, and vomiting.
Which TKI is Best?
Invited discussant Antonio Passaro, MD, PhD, from the European Institute of Oncology in Milan, noted that eligibility for treatment with savolitinib or other MET exon 14-targeting TKIs is limited to about 3% of patients with NSCLC of adenocarcinoma histology.
He said that savolitinib appears to be similar in performance to two other TKIs for NSCLC with MET exon-14 skipping mutations that are currently on the market in the United States, Europe, and Japan: capmatinib (Tabrecta) and tepotinib (Tepmetko).
“Globally, all the results show a numerically better performance when we use a selective TKI in first-line treatment over the second-line treatment, in particular for overall response rate,” he said.
Dr. Passaro noted that savolitinib differs from the other two MET TKIs in that PFS with savolitinib is similar for treatment-naive and previously treated patients.
He added, however, that “today it’s very difficult” to determine which is the “perfect” agent for a specific disease presentation, particularly since MET exon 14 skipping mutations can also be found in patients with squamous cell carcinomas and those with a history of smoking.
To get a better sense of which drug to use in a specific situation, it would be helpful to analyze trial results in the context of tumor histology, smoking history, programmed death protein 1-ligand 1 status, and co-mutations, he said.
The study was sponsored by Hutchmed. Dr. Zhang reported having no conflicts of interest. Dr. Passaro reported a consulting, advisory, or speakers bureau role for multiple companies, not including Hutchmed.
Savolitinib, a selective oral tyrosine kinase inhibitor, showed good activity against locally advanced or metastatic non–small cell lung cancer (NSCLC) bearing MET exon 14 mutations as both first-line therapy for treatment-naive patients and in second-line of therapy for previously treated patients
“The phase 3b study results further confirm savolitinib as a valuable targeted therapy option for naive and previously-treated non–small cell lung cancer with MET 14 exon mutations,” Yongchang Zhang, MD, said while presenting the final results of the trial at the European Lung Cancer Congress 2024.
For 87 previously untreated patients the objective response rate (ORR) as assessed by independent review, the primary endpoint, was 62.1%. For 79 patients receiving savolitinib in the second line, the ORR was 39.2%, reported Dr. Zhang, MD, of the Hunan Cancer Hospital in Changsha, China.
Preliminary results of this trial were reported at the World Conference on Lung Cancer in 2023.
Selective Inhibitor
Savolitinib (AZD6094, also called volitinib) is reported to be a highly selective oral inhibitor of the MET receptor tyrosine kinase (TKI). It is approved in China for the treatment of patients with NSCLC harboring MET exon 14 mutations that has progressed on prior systemic therapy, or patients who are unable to tolerate platinum-based chemotherapy.
In the phase 3b study, patients with MET ex14-positive tumors who were negative for EGFR, ALK or ROS1 alterations and were naive to a MET inhibitor were enrolled. Those who weighed 50 kg or greater received 600 mg savolitinib orally once daily for each 21-day cycle, while patients who weighed less than 50 kg received a 400-mg daily dose. Therapy continued until disease progression, death, or unacceptable toxicity.
Tumors were evaluated by investigators every 6 weeks for the first year, than every 12 weeks thereafter.
As noted before, ORR by independent review was 62.1% for treatment-naive patients and 39.2% for previously treated patients. The respective ORRs by investigator assessment were 59.8% and 43%. All responses in each arm were partial responses.
Median progression-free survival (PFS) after a median follow-up of 18 months for treatment-naive patients and 11 months for treatment-experienced patients was 13.7 months and 11 months, respectively.
Overall survival after a median follow-up of 20.8 months for treatment-naive patients and 12.5 months for previously treated patients was not reached in treatment-naive patients and not mature in treatment-experienced patients.
Grade 3 or greater treatment-emergent adverse events occurred in 74.1% of patients, including 3 events (1.8%) leading to death. Dose modifications were required for 74.7% of patients.
Grade 3 or greater adverse events included peripheral edema, liver enzyme elevations, abnormal liver function, decreased platelet and white blood cell counts, and vomiting.
Which TKI is Best?
Invited discussant Antonio Passaro, MD, PhD, from the European Institute of Oncology in Milan, noted that eligibility for treatment with savolitinib or other MET exon 14-targeting TKIs is limited to about 3% of patients with NSCLC of adenocarcinoma histology.
He said that savolitinib appears to be similar in performance to two other TKIs for NSCLC with MET exon-14 skipping mutations that are currently on the market in the United States, Europe, and Japan: capmatinib (Tabrecta) and tepotinib (Tepmetko).
“Globally, all the results show a numerically better performance when we use a selective TKI in first-line treatment over the second-line treatment, in particular for overall response rate,” he said.
Dr. Passaro noted that savolitinib differs from the other two MET TKIs in that PFS with savolitinib is similar for treatment-naive and previously treated patients.
He added, however, that “today it’s very difficult” to determine which is the “perfect” agent for a specific disease presentation, particularly since MET exon 14 skipping mutations can also be found in patients with squamous cell carcinomas and those with a history of smoking.
To get a better sense of which drug to use in a specific situation, it would be helpful to analyze trial results in the context of tumor histology, smoking history, programmed death protein 1-ligand 1 status, and co-mutations, he said.
The study was sponsored by Hutchmed. Dr. Zhang reported having no conflicts of interest. Dr. Passaro reported a consulting, advisory, or speakers bureau role for multiple companies, not including Hutchmed.
FROM ELCC 2024
New Guidance for the Treatment of Metastatic Breast Cancer
The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.
Where do the ABC International Consensus Guidelines come from?
The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?
Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
Can you tell me about the other issues discussed in the guidelines besides drugs?
For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?
The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.
Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.
We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.
We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
The ABC Guidelines discuss tough clinical situations. Can you explain?
The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.
It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
What other tough clinical situations do you discuss in the new guidelines?
We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.
It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.
Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.
We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?
A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.
It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.
Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.
We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.
Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.
Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?
In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.
Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.
The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.
Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.
Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.
A version of this article appeared on Medscape.com.
The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.
Where do the ABC International Consensus Guidelines come from?
The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?
Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
Can you tell me about the other issues discussed in the guidelines besides drugs?
For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?
The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.
Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.
We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.
We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
The ABC Guidelines discuss tough clinical situations. Can you explain?
The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.
It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
What other tough clinical situations do you discuss in the new guidelines?
We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.
It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.
Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.
We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?
A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.
It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.
Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.
We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.
Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.
Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?
In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.
Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.
The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.
Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.
Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.
A version of this article appeared on Medscape.com.
The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.
Where do the ABC International Consensus Guidelines come from?
The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?
Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
Can you tell me about the other issues discussed in the guidelines besides drugs?
For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?
The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.
Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.
We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.
We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
The ABC Guidelines discuss tough clinical situations. Can you explain?
The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.
It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
What other tough clinical situations do you discuss in the new guidelines?
We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.
It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.
Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.
We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?
A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.
It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.
Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.
We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.
Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.
Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?
In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.
Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.
The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.
Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.
Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.
A version of this article appeared on Medscape.com.
Few Childhood Cancer Survivors Get Recommended Screenings
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Minimally Invasive Cytoreductive Approach Comparable to Open Surgery for Ovarian Cancer
This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.
Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.
“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.
The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
Growing Use of MIS
Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).
Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
Outcomes Compared
Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.
As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.
Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.
Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.
Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.
As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).
There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.
The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
MIS Use Debatable: CON
Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.
In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.
“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.
Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.
Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.
In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.
Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.
She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.
MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
Debate: PRO
Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”
He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.
In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.
Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.
To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.
The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.
This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.
Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.
“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.
The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
Growing Use of MIS
Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).
Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
Outcomes Compared
Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.
As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.
Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.
Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.
Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.
As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).
There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.
The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
MIS Use Debatable: CON
Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.
In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.
“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.
Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.
Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.
In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.
Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.
She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.
MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
Debate: PRO
Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”
He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.
In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.
Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.
To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.
The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.
This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.
Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.
“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.
The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
Growing Use of MIS
Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).
Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
Outcomes Compared
Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.
As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.
Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.
Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.
Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.
As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).
There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.
The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
MIS Use Debatable: CON
Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.
In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.
“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.
Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.
Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.
In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.
Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.
She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.
MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
Debate: PRO
Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”
He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.
In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.
Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.
To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.
The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.
FROM SGO 2024
Subcutaneous Immunotherapy Promises Better Life For Cancer Patients
The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.
Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.
“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.
She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.
Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.
IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.
Participants were then asked what version they preferred and what they wanted to continue with.
Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.
When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.
The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.
The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.
The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).
Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.
When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.
The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.
The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.
Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.
“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.
She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.
Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.
IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.
Participants were then asked what version they preferred and what they wanted to continue with.
Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.
When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.
The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.
The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.
The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).
Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.
When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.
The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.
The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.
Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.
“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.
She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.
Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.
IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.
Participants were then asked what version they preferred and what they wanted to continue with.
Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.
When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.
The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.
The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.
The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).
Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.
When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.
The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.
FROM ELCC 2024