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FDA investigates secondary cancers from CAR T-cell therapies
Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.
Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.
Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.
Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).
“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.
Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
A version of this article first appeared on Medscape.com.
Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.
Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.
Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.
Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).
“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.
Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
A version of this article first appeared on Medscape.com.
Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.
Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.
Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.
Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).
“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.
Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
A version of this article first appeared on Medscape.com.
FDA OKs capivasertib for certain advanced breast cancers
Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.
The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.
Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.
Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.
In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).
An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.
Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.
The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.
A version of this article first appeared on Medscape.com.
Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.
The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.
Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.
Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.
In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).
An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.
Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.
The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.
A version of this article first appeared on Medscape.com.
Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.
The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.
Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.
Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.
In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).
An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.
Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.
The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.
A version of this article first appeared on Medscape.com.
FDA approves first tx for rare, deadly clotting disorder
Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.
The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.
The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.
Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.
Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.
The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.
“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”
A version of this article first appeared on Medscape.com.
Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.
The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.
The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.
Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.
Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.
The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.
“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”
A version of this article first appeared on Medscape.com.
Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.
The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.
The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.
Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.
Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.
The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.
“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”
A version of this article first appeared on Medscape.com.
Prior authorizations interfere with recommended cancer care
Of 178 respondents with a prior authorization (PA) experience, 39 (22%) did not receive the care recommended by their treatment team because of a PA requirement, and 123 (69%) experienced a delay in receiving the recommended care, Fumiko Chino, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported.
Reasons for not receiving recommended care included complete denial by the insurance company (26 of 39 patients), and a change in treatment plan because of initial denial (13 of 39 patients). Delays in receiving recommended care were 2 or more weeks for 90 of 123 patients, and 1 month or more in 40 of 123 patients.
Delays in receiving recommended care were associated with increased patient anxiety, a negative perception of the PA process, and patient administrative burden, the investigators noted.
The findings, which capture patient-based perspectives in the ongoing PA debacle, were reported online in JAMA Network Open.
“Prior authorization requires clinicians and patients to navigate a complex approval pathway. Resultant delays and denial can be particularly problematic for patients with cancer, who often need urgent treatment or symptom management,” the investigators explained. “Focusing on patient experiences with PA highlights a missing perspective in policy discussions and suggests another potential factor associated with eroding trust in the health care system.”
To assess the impact of PA, they conducted an anonymous survey using a convenience sample of patients with any cancer-related PA experience from July 1 to Oct. 6, 2022. Mean self-reported PA-related anxiety scores were 74.7 on a scale of 0-100, whereas usual anxiety scores were 37.5.
PA-related anxiety scores were significantly correlated with the length of treatment delay (P = .04), time spent on PA (P < .001), and overall PA experience (P < .001).
“Dealing with PA issues adds an extra layer of stress, which is known to increase anxiety and can worsen treatment-related and disease-related symptoms and adverse effects,” the investigators noted.
PA issues also eroded trust: 89% of respondents trusted their insurance company less, and 83% trusted the health care system less after a PA experience. Patient involvement in the PA process increased the likelihood of such distrust and of having a negative experience.
Of the 178 respondents, most were women (88%), non-Hispanic White individuals (84%), college graduates (84%), and young (18-39 years, 41%; 40-54 years, 33%). Most (67%) had to personally become involved in the PA process by calling their insurance or filing an appeal.
The investigators noted that “efforts to create national health policy solutions that streamline PA and make the process more transparent have been a major lobbying effort of large oncology societies,” and that bipartisan legislation to “establish regulations on the quality and timeliness of PA in the Medicare Advantage population” has stalled.
“In the meantime, the Centers for Medicare & Medicaid Services acted directly by issuing a final rule in April 2023 aimed at improving PA processes within the Medicare Advantage population by 2024,” they wrote, adding that “streamlining the PA process is key to optimizing the quality of care delivered and improving patients’ experience with cancer care.
“Policy interventions will be necessary to reform the PA process, as will advocacy efforts at the patient, clinician, and hospital level,” they concluded.
Chino reported funding through a National Institutes of Health/National Cancer Institute Cancer Center Support Grant.
Of 178 respondents with a prior authorization (PA) experience, 39 (22%) did not receive the care recommended by their treatment team because of a PA requirement, and 123 (69%) experienced a delay in receiving the recommended care, Fumiko Chino, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported.
Reasons for not receiving recommended care included complete denial by the insurance company (26 of 39 patients), and a change in treatment plan because of initial denial (13 of 39 patients). Delays in receiving recommended care were 2 or more weeks for 90 of 123 patients, and 1 month or more in 40 of 123 patients.
Delays in receiving recommended care were associated with increased patient anxiety, a negative perception of the PA process, and patient administrative burden, the investigators noted.
The findings, which capture patient-based perspectives in the ongoing PA debacle, were reported online in JAMA Network Open.
“Prior authorization requires clinicians and patients to navigate a complex approval pathway. Resultant delays and denial can be particularly problematic for patients with cancer, who often need urgent treatment or symptom management,” the investigators explained. “Focusing on patient experiences with PA highlights a missing perspective in policy discussions and suggests another potential factor associated with eroding trust in the health care system.”
To assess the impact of PA, they conducted an anonymous survey using a convenience sample of patients with any cancer-related PA experience from July 1 to Oct. 6, 2022. Mean self-reported PA-related anxiety scores were 74.7 on a scale of 0-100, whereas usual anxiety scores were 37.5.
PA-related anxiety scores were significantly correlated with the length of treatment delay (P = .04), time spent on PA (P < .001), and overall PA experience (P < .001).
“Dealing with PA issues adds an extra layer of stress, which is known to increase anxiety and can worsen treatment-related and disease-related symptoms and adverse effects,” the investigators noted.
PA issues also eroded trust: 89% of respondents trusted their insurance company less, and 83% trusted the health care system less after a PA experience. Patient involvement in the PA process increased the likelihood of such distrust and of having a negative experience.
Of the 178 respondents, most were women (88%), non-Hispanic White individuals (84%), college graduates (84%), and young (18-39 years, 41%; 40-54 years, 33%). Most (67%) had to personally become involved in the PA process by calling their insurance or filing an appeal.
The investigators noted that “efforts to create national health policy solutions that streamline PA and make the process more transparent have been a major lobbying effort of large oncology societies,” and that bipartisan legislation to “establish regulations on the quality and timeliness of PA in the Medicare Advantage population” has stalled.
“In the meantime, the Centers for Medicare & Medicaid Services acted directly by issuing a final rule in April 2023 aimed at improving PA processes within the Medicare Advantage population by 2024,” they wrote, adding that “streamlining the PA process is key to optimizing the quality of care delivered and improving patients’ experience with cancer care.
“Policy interventions will be necessary to reform the PA process, as will advocacy efforts at the patient, clinician, and hospital level,” they concluded.
Chino reported funding through a National Institutes of Health/National Cancer Institute Cancer Center Support Grant.
Of 178 respondents with a prior authorization (PA) experience, 39 (22%) did not receive the care recommended by their treatment team because of a PA requirement, and 123 (69%) experienced a delay in receiving the recommended care, Fumiko Chino, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported.
Reasons for not receiving recommended care included complete denial by the insurance company (26 of 39 patients), and a change in treatment plan because of initial denial (13 of 39 patients). Delays in receiving recommended care were 2 or more weeks for 90 of 123 patients, and 1 month or more in 40 of 123 patients.
Delays in receiving recommended care were associated with increased patient anxiety, a negative perception of the PA process, and patient administrative burden, the investigators noted.
The findings, which capture patient-based perspectives in the ongoing PA debacle, were reported online in JAMA Network Open.
“Prior authorization requires clinicians and patients to navigate a complex approval pathway. Resultant delays and denial can be particularly problematic for patients with cancer, who often need urgent treatment or symptom management,” the investigators explained. “Focusing on patient experiences with PA highlights a missing perspective in policy discussions and suggests another potential factor associated with eroding trust in the health care system.”
To assess the impact of PA, they conducted an anonymous survey using a convenience sample of patients with any cancer-related PA experience from July 1 to Oct. 6, 2022. Mean self-reported PA-related anxiety scores were 74.7 on a scale of 0-100, whereas usual anxiety scores were 37.5.
PA-related anxiety scores were significantly correlated with the length of treatment delay (P = .04), time spent on PA (P < .001), and overall PA experience (P < .001).
“Dealing with PA issues adds an extra layer of stress, which is known to increase anxiety and can worsen treatment-related and disease-related symptoms and adverse effects,” the investigators noted.
PA issues also eroded trust: 89% of respondents trusted their insurance company less, and 83% trusted the health care system less after a PA experience. Patient involvement in the PA process increased the likelihood of such distrust and of having a negative experience.
Of the 178 respondents, most were women (88%), non-Hispanic White individuals (84%), college graduates (84%), and young (18-39 years, 41%; 40-54 years, 33%). Most (67%) had to personally become involved in the PA process by calling their insurance or filing an appeal.
The investigators noted that “efforts to create national health policy solutions that streamline PA and make the process more transparent have been a major lobbying effort of large oncology societies,” and that bipartisan legislation to “establish regulations on the quality and timeliness of PA in the Medicare Advantage population” has stalled.
“In the meantime, the Centers for Medicare & Medicaid Services acted directly by issuing a final rule in April 2023 aimed at improving PA processes within the Medicare Advantage population by 2024,” they wrote, adding that “streamlining the PA process is key to optimizing the quality of care delivered and improving patients’ experience with cancer care.
“Policy interventions will be necessary to reform the PA process, as will advocacy efforts at the patient, clinician, and hospital level,” they concluded.
Chino reported funding through a National Institutes of Health/National Cancer Institute Cancer Center Support Grant.
FROM JAMA NETWORK OPEN
T-DXd benefits persist for HER2-low breast cancer
and low HER2 expression in the randomized phase 3 DESTINY-Breast04 study, according to 32-month follow-up data.
The overall safety profile of the HER2-directed antibody drug conjugate was also comparable to that observed at the primary analysis in 2022, and longer exposure did not appear to increase toxicity, Shanu Modi, MD, reported on behalf of the DESTINY-Breast04 investigators at the European Society of Medical Oncology (ESMO) Congress 2023.
“These results continue to support the use of T-DXd as the new standard of care after one line of chemotherapy in patients with HER2-low metastatic breast cancer,” said Dr. Modi, a breast oncologist and attending physician at Memorial Sloan Kettering Cancer Center, New York.
DESTINY-Breast04 enrolled 557 patients 2:1 to receive 5.4 mg/kg of T-DXd every 3 weeks or physicians’ choice of capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel, and established HER2-low mBC as “a new targetable patient population with T-DXd as a new standard of care,” she explained.
Median overall survival (mOS) with a median of 18.4 months of follow-up at the Jan. 11, 2022, primary data cut-off was 23.4 months in the T-DXd arm versus 16.8 months in the TPC arm and 23.9 versus 17.5 months, respectively, in the hormone receptor–positive (HR+) cohort (hazard ratio, 0.64 for both groups). At the preplanned extended follow-up with data cut-off on March 1, 2023, the mOS was 22.9 versus 16.8 months for T-DXd versus TPC, and 23.9 versus 17.6 months for the HR+ cohort, respectively (HR, 0.69 for both).
Median progression-free survival (PFS) by investigator assessment was 8.8 versus 4.2 months for the full cohort, and 9.6 versus 4.2 months for the HR+ cohort (HR, 0.36 and 0.37, respectively). PFS was consistent with the results from the primary analysis.
The benefits in the HR+ patients were consistent across all patient subgroups, Dr. Modi noted.
“I do think it’s interesting to point out that at the landmark 2-year point, all patients on standard chemotherapy discontinued study treatment, whereas 15% on T-DXd remain [on treatment] without any evidence of disease progression, Dr. Modi added
An exploratory analysis in the hormone receptor–negative (HR–) cohort showed mOS of 18.2 versus 8.3 months at the primary analysis (HR, 0.48), and a “clinically meaningful and numerical advantage for T-DXd” persisted at the planned follow-up (mOS, 17.1 vs. 8.3; HR, 0.58), she said.
PFS in the HR- cohort was 8.5 versus 2.9 months at the primary analysis, and 6.3 versus 2.9 months at the update (HR, 0.46 and 0.29, respectively).
An assessment of post-study therapies received by patients showed that those therapies did not account for the significant survival advantage conferred by T-DXd, Dr. Modi said.
She noted, however, that while no new safety signals were observed at follow-up, lung toxicity remains a “toxicity of special interest,” having occurred in 12.1% of cases at the time of the primary analysis.
Most cases were grade 1 or 2, and no new cases were observed at follow-up, but one patient with lung toxicity and an initial grade 3 event experienced clinical deterioration and later died from lung toxicity, which underscores the importance of remaining vigilant and intervening promptly in all cases of lung toxicity, Dr. Modi stressed.
Invited discussant Giampaolo Bianchini, MD, reiterated that T-DXd is an effective treatment option and said, “we must accurately identify patients and avoid improperly denying this important therapeutic option.”
Although HER2-low disease is not a unique biological disease entity, it is a “practical and pragmatic definition used to select patients with ‘some degree’ of HER2 protein expression adopting a test and a scoring system already implemented in the routine clinical practice,” said Dr. Bianchini, head of the breast cancer group and head of clinical translational and immunotherapy research at IRCCS Ospedale, San Raffaele, Milan.
However, the current definition may be inadequate, he said, explaining that the ongoing DESTINY-Breast06 study “will challenge the current definition of what we consider HER2-low definition,” potentially extending the T-DXd indication to HER2 ultra-low.
Furthermore, current HER2 testing was designed to discriminate cases with high abundant protein – not for the low HER2 dynamic range, which leads to technical inaccuracy.
Given these considerations, he suggested considering a new biopsy, if feasible, in patients with an immunohistochemistry (IHC) score of 0 in all tumor biopsies, and having a revision performed by the pathologist.
In patients with an IHC score of 1 or greater only in one biopsy, there is no need to confirm the HER2-low status, he said.
DESTINY-Breast04 is funded by Daiichi Sankyo Inc. and AstraZeneca. Dr. Modi reported relationships with Daiichi Sankyo, Genentech, AstraZeneca, Seagen, and MacroGenics. Dr. Bianchini reported relationships with AstraZeneca, Daiichi Sankyo, Gilead, MSD, Seagen, Roche, Sanofi, Lilly, EISAI, Novartis, Pfizer, Stemline, Exact Science, and Agendia.
and low HER2 expression in the randomized phase 3 DESTINY-Breast04 study, according to 32-month follow-up data.
The overall safety profile of the HER2-directed antibody drug conjugate was also comparable to that observed at the primary analysis in 2022, and longer exposure did not appear to increase toxicity, Shanu Modi, MD, reported on behalf of the DESTINY-Breast04 investigators at the European Society of Medical Oncology (ESMO) Congress 2023.
“These results continue to support the use of T-DXd as the new standard of care after one line of chemotherapy in patients with HER2-low metastatic breast cancer,” said Dr. Modi, a breast oncologist and attending physician at Memorial Sloan Kettering Cancer Center, New York.
DESTINY-Breast04 enrolled 557 patients 2:1 to receive 5.4 mg/kg of T-DXd every 3 weeks or physicians’ choice of capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel, and established HER2-low mBC as “a new targetable patient population with T-DXd as a new standard of care,” she explained.
Median overall survival (mOS) with a median of 18.4 months of follow-up at the Jan. 11, 2022, primary data cut-off was 23.4 months in the T-DXd arm versus 16.8 months in the TPC arm and 23.9 versus 17.5 months, respectively, in the hormone receptor–positive (HR+) cohort (hazard ratio, 0.64 for both groups). At the preplanned extended follow-up with data cut-off on March 1, 2023, the mOS was 22.9 versus 16.8 months for T-DXd versus TPC, and 23.9 versus 17.6 months for the HR+ cohort, respectively (HR, 0.69 for both).
Median progression-free survival (PFS) by investigator assessment was 8.8 versus 4.2 months for the full cohort, and 9.6 versus 4.2 months for the HR+ cohort (HR, 0.36 and 0.37, respectively). PFS was consistent with the results from the primary analysis.
The benefits in the HR+ patients were consistent across all patient subgroups, Dr. Modi noted.
“I do think it’s interesting to point out that at the landmark 2-year point, all patients on standard chemotherapy discontinued study treatment, whereas 15% on T-DXd remain [on treatment] without any evidence of disease progression, Dr. Modi added
An exploratory analysis in the hormone receptor–negative (HR–) cohort showed mOS of 18.2 versus 8.3 months at the primary analysis (HR, 0.48), and a “clinically meaningful and numerical advantage for T-DXd” persisted at the planned follow-up (mOS, 17.1 vs. 8.3; HR, 0.58), she said.
PFS in the HR- cohort was 8.5 versus 2.9 months at the primary analysis, and 6.3 versus 2.9 months at the update (HR, 0.46 and 0.29, respectively).
An assessment of post-study therapies received by patients showed that those therapies did not account for the significant survival advantage conferred by T-DXd, Dr. Modi said.
She noted, however, that while no new safety signals were observed at follow-up, lung toxicity remains a “toxicity of special interest,” having occurred in 12.1% of cases at the time of the primary analysis.
Most cases were grade 1 or 2, and no new cases were observed at follow-up, but one patient with lung toxicity and an initial grade 3 event experienced clinical deterioration and later died from lung toxicity, which underscores the importance of remaining vigilant and intervening promptly in all cases of lung toxicity, Dr. Modi stressed.
Invited discussant Giampaolo Bianchini, MD, reiterated that T-DXd is an effective treatment option and said, “we must accurately identify patients and avoid improperly denying this important therapeutic option.”
Although HER2-low disease is not a unique biological disease entity, it is a “practical and pragmatic definition used to select patients with ‘some degree’ of HER2 protein expression adopting a test and a scoring system already implemented in the routine clinical practice,” said Dr. Bianchini, head of the breast cancer group and head of clinical translational and immunotherapy research at IRCCS Ospedale, San Raffaele, Milan.
However, the current definition may be inadequate, he said, explaining that the ongoing DESTINY-Breast06 study “will challenge the current definition of what we consider HER2-low definition,” potentially extending the T-DXd indication to HER2 ultra-low.
Furthermore, current HER2 testing was designed to discriminate cases with high abundant protein – not for the low HER2 dynamic range, which leads to technical inaccuracy.
Given these considerations, he suggested considering a new biopsy, if feasible, in patients with an immunohistochemistry (IHC) score of 0 in all tumor biopsies, and having a revision performed by the pathologist.
In patients with an IHC score of 1 or greater only in one biopsy, there is no need to confirm the HER2-low status, he said.
DESTINY-Breast04 is funded by Daiichi Sankyo Inc. and AstraZeneca. Dr. Modi reported relationships with Daiichi Sankyo, Genentech, AstraZeneca, Seagen, and MacroGenics. Dr. Bianchini reported relationships with AstraZeneca, Daiichi Sankyo, Gilead, MSD, Seagen, Roche, Sanofi, Lilly, EISAI, Novartis, Pfizer, Stemline, Exact Science, and Agendia.
and low HER2 expression in the randomized phase 3 DESTINY-Breast04 study, according to 32-month follow-up data.
The overall safety profile of the HER2-directed antibody drug conjugate was also comparable to that observed at the primary analysis in 2022, and longer exposure did not appear to increase toxicity, Shanu Modi, MD, reported on behalf of the DESTINY-Breast04 investigators at the European Society of Medical Oncology (ESMO) Congress 2023.
“These results continue to support the use of T-DXd as the new standard of care after one line of chemotherapy in patients with HER2-low metastatic breast cancer,” said Dr. Modi, a breast oncologist and attending physician at Memorial Sloan Kettering Cancer Center, New York.
DESTINY-Breast04 enrolled 557 patients 2:1 to receive 5.4 mg/kg of T-DXd every 3 weeks or physicians’ choice of capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel, and established HER2-low mBC as “a new targetable patient population with T-DXd as a new standard of care,” she explained.
Median overall survival (mOS) with a median of 18.4 months of follow-up at the Jan. 11, 2022, primary data cut-off was 23.4 months in the T-DXd arm versus 16.8 months in the TPC arm and 23.9 versus 17.5 months, respectively, in the hormone receptor–positive (HR+) cohort (hazard ratio, 0.64 for both groups). At the preplanned extended follow-up with data cut-off on March 1, 2023, the mOS was 22.9 versus 16.8 months for T-DXd versus TPC, and 23.9 versus 17.6 months for the HR+ cohort, respectively (HR, 0.69 for both).
Median progression-free survival (PFS) by investigator assessment was 8.8 versus 4.2 months for the full cohort, and 9.6 versus 4.2 months for the HR+ cohort (HR, 0.36 and 0.37, respectively). PFS was consistent with the results from the primary analysis.
The benefits in the HR+ patients were consistent across all patient subgroups, Dr. Modi noted.
“I do think it’s interesting to point out that at the landmark 2-year point, all patients on standard chemotherapy discontinued study treatment, whereas 15% on T-DXd remain [on treatment] without any evidence of disease progression, Dr. Modi added
An exploratory analysis in the hormone receptor–negative (HR–) cohort showed mOS of 18.2 versus 8.3 months at the primary analysis (HR, 0.48), and a “clinically meaningful and numerical advantage for T-DXd” persisted at the planned follow-up (mOS, 17.1 vs. 8.3; HR, 0.58), she said.
PFS in the HR- cohort was 8.5 versus 2.9 months at the primary analysis, and 6.3 versus 2.9 months at the update (HR, 0.46 and 0.29, respectively).
An assessment of post-study therapies received by patients showed that those therapies did not account for the significant survival advantage conferred by T-DXd, Dr. Modi said.
She noted, however, that while no new safety signals were observed at follow-up, lung toxicity remains a “toxicity of special interest,” having occurred in 12.1% of cases at the time of the primary analysis.
Most cases were grade 1 or 2, and no new cases were observed at follow-up, but one patient with lung toxicity and an initial grade 3 event experienced clinical deterioration and later died from lung toxicity, which underscores the importance of remaining vigilant and intervening promptly in all cases of lung toxicity, Dr. Modi stressed.
Invited discussant Giampaolo Bianchini, MD, reiterated that T-DXd is an effective treatment option and said, “we must accurately identify patients and avoid improperly denying this important therapeutic option.”
Although HER2-low disease is not a unique biological disease entity, it is a “practical and pragmatic definition used to select patients with ‘some degree’ of HER2 protein expression adopting a test and a scoring system already implemented in the routine clinical practice,” said Dr. Bianchini, head of the breast cancer group and head of clinical translational and immunotherapy research at IRCCS Ospedale, San Raffaele, Milan.
However, the current definition may be inadequate, he said, explaining that the ongoing DESTINY-Breast06 study “will challenge the current definition of what we consider HER2-low definition,” potentially extending the T-DXd indication to HER2 ultra-low.
Furthermore, current HER2 testing was designed to discriminate cases with high abundant protein – not for the low HER2 dynamic range, which leads to technical inaccuracy.
Given these considerations, he suggested considering a new biopsy, if feasible, in patients with an immunohistochemistry (IHC) score of 0 in all tumor biopsies, and having a revision performed by the pathologist.
In patients with an IHC score of 1 or greater only in one biopsy, there is no need to confirm the HER2-low status, he said.
DESTINY-Breast04 is funded by Daiichi Sankyo Inc. and AstraZeneca. Dr. Modi reported relationships with Daiichi Sankyo, Genentech, AstraZeneca, Seagen, and MacroGenics. Dr. Bianchini reported relationships with AstraZeneca, Daiichi Sankyo, Gilead, MSD, Seagen, Roche, Sanofi, Lilly, EISAI, Novartis, Pfizer, Stemline, Exact Science, and Agendia.
FROM ESMO 2023
ALK inhibitor alectinib shows DFS benefit in early NSCLC
Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.
The , said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.
ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.
The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.
The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.
At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).
Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).
The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.
Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.
“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.
Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”
“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.
Chemotherapy, conversely, has been shown to improve overall survival, she noted.
Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.
“So, I think we should still wait for more results from this trial,” she said.
In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”
The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.
A version of this article first appeared on Medscape.com.
Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.
The , said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.
ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.
The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.
The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.
At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).
Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).
The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.
Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.
“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.
Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”
“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.
Chemotherapy, conversely, has been shown to improve overall survival, she noted.
Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.
“So, I think we should still wait for more results from this trial,” she said.
In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”
The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.
A version of this article first appeared on Medscape.com.
Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.
The , said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.
ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.
The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.
The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.
At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).
Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).
The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.
Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.
“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.
Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”
“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.
Chemotherapy, conversely, has been shown to improve overall survival, she noted.
Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.
“So, I think we should still wait for more results from this trial,” she said.
In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”
The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.
A version of this article first appeared on Medscape.com.
FROM ESMO CONGRESS 2023
Perioperative nivolumab improves EFS in resectable NSCLC
Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.
In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.
“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.
Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.
This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.
The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.
Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).
The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).
Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.
In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.
No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.
Despite the promising findings, some questions remain, said Dr. Garassino.
First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.
So, “the answer is yes, we should treat” these patients, she said.
But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”
CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.
A version of this article first appeared on Medscape.com.
Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.
In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.
“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.
Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.
This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.
The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.
Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).
The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).
Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.
In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.
No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.
Despite the promising findings, some questions remain, said Dr. Garassino.
First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.
So, “the answer is yes, we should treat” these patients, she said.
But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”
CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.
A version of this article first appeared on Medscape.com.
Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.
In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.
“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.
Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.
This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.
The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.
Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).
The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).
Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.
In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.
No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.
Despite the promising findings, some questions remain, said Dr. Garassino.
First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.
So, “the answer is yes, we should treat” these patients, she said.
But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”
CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.
A version of this article first appeared on Medscape.com.
FROM ESMO CONGRESS 2023
FDA approves nivolumab for resected stage IIB/C melanoma
The , expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.
Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.
The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.
Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.
Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.
The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.
Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.
A version of this article appeared on Medscape.com.
The , expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.
Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.
The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.
Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.
Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.
The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.
Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.
A version of this article appeared on Medscape.com.
The , expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.
Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.
The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.
Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.
Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.
The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.
Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.
A version of this article appeared on Medscape.com.
What the first authorized DNA cancer risk test can and can’t tell you
A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.
The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.
Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
How the test system works
Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.
Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.
Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.
Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
What the test can do
Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.
The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.
“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
What the test can’t do
The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing.
For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.
“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
Test safety
Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.
A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.
“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.
Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
Public health implications
The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.
The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.
A version of this article first appeared on Medscape.com.
A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.
The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.
Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
How the test system works
Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.
Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.
Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.
Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
What the test can do
Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.
The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.
“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
What the test can’t do
The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing.
For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.
“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
Test safety
Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.
A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.
“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.
Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
Public health implications
The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.
The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.
A version of this article first appeared on Medscape.com.
A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.
The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.
Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
How the test system works
Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.
Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.
Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.
Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
What the test can do
Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.
The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.
“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
What the test can’t do
The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing.
For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.
“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
Test safety
Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.
A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.
“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.
Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
Public health implications
The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.
The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.
A version of this article first appeared on Medscape.com.
MOC opposition continues to gain momentum as ASH weighs in
ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.
“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.
Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”
The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.
The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”
The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.
The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.
In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.
On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.
The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”
After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”
A version of this article first appeared on Medscape.com.
ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.
“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.
Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”
The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.
The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”
The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.
The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.
In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.
On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.
The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”
After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”
A version of this article first appeared on Medscape.com.
ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.
“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.
Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”
The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.
The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”
The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.
The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.
In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.
On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.
The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”
After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”
A version of this article first appeared on Medscape.com.