ASCO Breast Cancer

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

A version of this article first appeared on Medscape.com.

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

A version of this article first appeared on Medscape.com.

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

A version of this article first appeared on Medscape.com.

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

A version of this article first appeared on Medscape.com.

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

A version of this article first appeared on Medscape.com.

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

A version of this article first appeared on Medscape.com.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

For women with early-stage estrogen-receptor positive breast cancer, adjuvant endocrine therapy is known to decrease the likelihood of recurrence and improve survival, while omitting the therapy is associated with a higher risk of death.

For that reason, current guidelines, including those from the National Comprehensive Cancer Network, recommend adjuvant endocrine therapy (AET) for patients with estrogen-receptor positive (ER+) breast cancers.

But these and other guidelines do not make recommendations for a class of tumors deemed estrogen receptor low positive, often referred to as “ER-low,” a category in which ER is seen expressed in between 1% and 10% of cells. This is because benefits of endocrine therapy have not been demonstrated in patients with ER-low disease.

New research presented at the annual meeting of the American Society of Clinical Oncology in Chicago may change how clinicians and patients think about endocrine therapy. The findings showed that omitting endocrine therapy after surgery and chemotherapy was associated with a 25% higher chance of death within 3 years in ER-low patients.

Endocrine therapy, the investigators say, should therefore be offered to all patients with ER-low cancers, at least until it can be determined which subgroups are most likely to benefit.

How Was the Study Conducted?

Grace M. Choong, MD, of the Mayo Clinic in Rochester, Minnesota, and her colleagues, looked at 2018-2020 data from the National Cancer Database for more than 350,000 female patients with stages 1-3, ER+ breast cancer. From among these they identified about 7000 patients with ER-low cancers who had undergone adjuvant or neoadjuvant chemotherapy.

“We specifically wanted to focus on those treated with chemotherapy as these patients have a higher risk of recurrence in our short interval follow-up,” Dr. Choong said during her presentation.

Patients’ median age was 55 years, and three-quarters of them were White. Their tumors were more likely to be HER2-negative (65%), PR-negative (73%), have higher Ki-67 expression, and have a higher clinical stage (73% grade III).

Forty-two percent of patients did not undergo AET as part of their treatment regimen, with various tumor factors seen associated with AET omission. At a median 3 years of follow-up, 586 patients had died. After the researchers controlled for age, comorbidities, year of diagnosis, tumor factors, and pathologic stage, the effect of omitting AET still resulted in significantly worse survival: (HR 1.25, 95% CI: 1.05-1.48, P = .01).

Mortality was driven by patients with residual disease after neoadjuvant chemotherapy, who comprised nearly half the study cohort. In these patients, omission of endocrine therapy was associated with a 27% higher risk of death (HR 1.27, 1.10-1.58). However, for those with a complete pathological response following chemotherapy, omission of endocrine therapy was not associated with a higher risk of death (HR 1.06; 0.62-1.80).

The investigators noted several limitations of their study, including a retrospective design and no information available on recurrence or the duration of endocrine therapy.
 

Why Is Endocrine Therapy So Frequently Omitted in This Patient Group?

Matthew P. Goetz, MD, of the Mayo Clinic, the study’s corresponding author, said in an interview that in Sweden, for example, ER-low patients are explicitly not offered endocrine therapy based on Swedish guidelines.

In other settings, he said, it is unclear what is happening.

“Are patients refusing it? Do physicians not even offer it because they think there is no value? We do not have that granular detail, but our data right now suggests a physician should be having this conversation with patients,” he said.
 

Which ER-Low Patients Are Likely To Benefit?

The findings apply mostly to patients with residual disease after chemotherapy, and underlying biological factors are likely the reason, Dr. Goetz said.

ER-low patients are a heterogeneous group, he explained.

“In genomic profiling, where we look at the underlying biology of these cancers, most of the ER-low cancers are considered the basal subtype of triple negative breast cancer. Those patients should have absolutely zero benefit from endocrine therapy. But there is another group, referred to as the luminal group, which comprises anywhere from 20% to 30% of the ER-low patients.”

Dr. Goetz said he expects to find that this latter group are the patients benefiting from endocrine therapy when they have residual disease.

“We are not yet at the point of saying to patients, ‘you have residual disease after chemotherapy. Let’s check your tumor to see if it is the basal or luminal subtype.’ But that is something that we are planning to look into. What is most important right now is that clinicians be aware of these data, and that there is a suggestion that omitting endocrine therapy may have detrimental effects on survival in this subgroup of patients.”
 

Are the Findings Compelling Enough To Change Clinical Practice Right Away?

In an interview about the findings, Eric Winer, MD, of the Yale Cancer Center in New Haven, Connecticut, cautioned that due to the retrospective study design, “we don’t know how doctors made decisions about who got endocrine therapy and who didn’t.”

The patients with the worst tumors tended not to get endocrine therapy, Dr. Winer noted, and despite attempts to adjust for this, “in any large data set like this, unlike in a randomized trial, you just can’t control for all the bias.”
 

What Should Doctors Tell Patients?

“In the setting of significant side effects from endocrine therapy, we’re still less certain about the benefits of endocrine therapy here than in somebody with an ER-high tumor,” Dr. Winer cautioned.

Nonetheless, he said, the new findings certainly suggest that there may be a benefit for endocrine therapy in patients with ER-low tumors, and doctors should make this known to patients. “It may not be the strongest evidence, but it’s evidence,” he said. “This is very much a question to be raised between the doctor and the patient.”

Dr. Choong and colleagues’ study was funded by a Mayo Clinic Breast Cancer SPORE grant. Dr. Goetz reported consulting fees and research support from pharmaceutical manufacturers, including AstraZeneca, Pfizer, Lilly, and Novartis. Dr. Choong and Dr. Winer reported no financial conflicts of interest.

For women with early-stage estrogen-receptor positive breast cancer, adjuvant endocrine therapy is known to decrease the likelihood of recurrence and improve survival, while omitting the therapy is associated with a higher risk of death.

For that reason, current guidelines, including those from the National Comprehensive Cancer Network, recommend adjuvant endocrine therapy (AET) for patients with estrogen-receptor positive (ER+) breast cancers.

But these and other guidelines do not make recommendations for a class of tumors deemed estrogen receptor low positive, often referred to as “ER-low,” a category in which ER is seen expressed in between 1% and 10% of cells. This is because benefits of endocrine therapy have not been demonstrated in patients with ER-low disease.

New research presented at the annual meeting of the American Society of Clinical Oncology in Chicago may change how clinicians and patients think about endocrine therapy. The findings showed that omitting endocrine therapy after surgery and chemotherapy was associated with a 25% higher chance of death within 3 years in ER-low patients.

Endocrine therapy, the investigators say, should therefore be offered to all patients with ER-low cancers, at least until it can be determined which subgroups are most likely to benefit.

How Was the Study Conducted?

Grace M. Choong, MD, of the Mayo Clinic in Rochester, Minnesota, and her colleagues, looked at 2018-2020 data from the National Cancer Database for more than 350,000 female patients with stages 1-3, ER+ breast cancer. From among these they identified about 7000 patients with ER-low cancers who had undergone adjuvant or neoadjuvant chemotherapy.

“We specifically wanted to focus on those treated with chemotherapy as these patients have a higher risk of recurrence in our short interval follow-up,” Dr. Choong said during her presentation.

Patients’ median age was 55 years, and three-quarters of them were White. Their tumors were more likely to be HER2-negative (65%), PR-negative (73%), have higher Ki-67 expression, and have a higher clinical stage (73% grade III).

Forty-two percent of patients did not undergo AET as part of their treatment regimen, with various tumor factors seen associated with AET omission. At a median 3 years of follow-up, 586 patients had died. After the researchers controlled for age, comorbidities, year of diagnosis, tumor factors, and pathologic stage, the effect of omitting AET still resulted in significantly worse survival: (HR 1.25, 95% CI: 1.05-1.48, P = .01).

Mortality was driven by patients with residual disease after neoadjuvant chemotherapy, who comprised nearly half the study cohort. In these patients, omission of endocrine therapy was associated with a 27% higher risk of death (HR 1.27, 1.10-1.58). However, for those with a complete pathological response following chemotherapy, omission of endocrine therapy was not associated with a higher risk of death (HR 1.06; 0.62-1.80).

The investigators noted several limitations of their study, including a retrospective design and no information available on recurrence or the duration of endocrine therapy.
 

Why Is Endocrine Therapy So Frequently Omitted in This Patient Group?

Matthew P. Goetz, MD, of the Mayo Clinic, the study’s corresponding author, said in an interview that in Sweden, for example, ER-low patients are explicitly not offered endocrine therapy based on Swedish guidelines.

In other settings, he said, it is unclear what is happening.

“Are patients refusing it? Do physicians not even offer it because they think there is no value? We do not have that granular detail, but our data right now suggests a physician should be having this conversation with patients,” he said.
 

Which ER-Low Patients Are Likely To Benefit?

The findings apply mostly to patients with residual disease after chemotherapy, and underlying biological factors are likely the reason, Dr. Goetz said.

ER-low patients are a heterogeneous group, he explained.

“In genomic profiling, where we look at the underlying biology of these cancers, most of the ER-low cancers are considered the basal subtype of triple negative breast cancer. Those patients should have absolutely zero benefit from endocrine therapy. But there is another group, referred to as the luminal group, which comprises anywhere from 20% to 30% of the ER-low patients.”

Dr. Goetz said he expects to find that this latter group are the patients benefiting from endocrine therapy when they have residual disease.

“We are not yet at the point of saying to patients, ‘you have residual disease after chemotherapy. Let’s check your tumor to see if it is the basal or luminal subtype.’ But that is something that we are planning to look into. What is most important right now is that clinicians be aware of these data, and that there is a suggestion that omitting endocrine therapy may have detrimental effects on survival in this subgroup of patients.”
 

Are the Findings Compelling Enough To Change Clinical Practice Right Away?

In an interview about the findings, Eric Winer, MD, of the Yale Cancer Center in New Haven, Connecticut, cautioned that due to the retrospective study design, “we don’t know how doctors made decisions about who got endocrine therapy and who didn’t.”

The patients with the worst tumors tended not to get endocrine therapy, Dr. Winer noted, and despite attempts to adjust for this, “in any large data set like this, unlike in a randomized trial, you just can’t control for all the bias.”
 

What Should Doctors Tell Patients?

“In the setting of significant side effects from endocrine therapy, we’re still less certain about the benefits of endocrine therapy here than in somebody with an ER-high tumor,” Dr. Winer cautioned.

Nonetheless, he said, the new findings certainly suggest that there may be a benefit for endocrine therapy in patients with ER-low tumors, and doctors should make this known to patients. “It may not be the strongest evidence, but it’s evidence,” he said. “This is very much a question to be raised between the doctor and the patient.”

Dr. Choong and colleagues’ study was funded by a Mayo Clinic Breast Cancer SPORE grant. Dr. Goetz reported consulting fees and research support from pharmaceutical manufacturers, including AstraZeneca, Pfizer, Lilly, and Novartis. Dr. Choong and Dr. Winer reported no financial conflicts of interest.

For women with early-stage estrogen-receptor positive breast cancer, adjuvant endocrine therapy is known to decrease the likelihood of recurrence and improve survival, while omitting the therapy is associated with a higher risk of death.

For that reason, current guidelines, including those from the National Comprehensive Cancer Network, recommend adjuvant endocrine therapy (AET) for patients with estrogen-receptor positive (ER+) breast cancers.

But these and other guidelines do not make recommendations for a class of tumors deemed estrogen receptor low positive, often referred to as “ER-low,” a category in which ER is seen expressed in between 1% and 10% of cells. This is because benefits of endocrine therapy have not been demonstrated in patients with ER-low disease.

New research presented at the annual meeting of the American Society of Clinical Oncology in Chicago may change how clinicians and patients think about endocrine therapy. The findings showed that omitting endocrine therapy after surgery and chemotherapy was associated with a 25% higher chance of death within 3 years in ER-low patients.

Endocrine therapy, the investigators say, should therefore be offered to all patients with ER-low cancers, at least until it can be determined which subgroups are most likely to benefit.

How Was the Study Conducted?

Grace M. Choong, MD, of the Mayo Clinic in Rochester, Minnesota, and her colleagues, looked at 2018-2020 data from the National Cancer Database for more than 350,000 female patients with stages 1-3, ER+ breast cancer. From among these they identified about 7000 patients with ER-low cancers who had undergone adjuvant or neoadjuvant chemotherapy.

“We specifically wanted to focus on those treated with chemotherapy as these patients have a higher risk of recurrence in our short interval follow-up,” Dr. Choong said during her presentation.

Patients’ median age was 55 years, and three-quarters of them were White. Their tumors were more likely to be HER2-negative (65%), PR-negative (73%), have higher Ki-67 expression, and have a higher clinical stage (73% grade III).

Forty-two percent of patients did not undergo AET as part of their treatment regimen, with various tumor factors seen associated with AET omission. At a median 3 years of follow-up, 586 patients had died. After the researchers controlled for age, comorbidities, year of diagnosis, tumor factors, and pathologic stage, the effect of omitting AET still resulted in significantly worse survival: (HR 1.25, 95% CI: 1.05-1.48, P = .01).

Mortality was driven by patients with residual disease after neoadjuvant chemotherapy, who comprised nearly half the study cohort. In these patients, omission of endocrine therapy was associated with a 27% higher risk of death (HR 1.27, 1.10-1.58). However, for those with a complete pathological response following chemotherapy, omission of endocrine therapy was not associated with a higher risk of death (HR 1.06; 0.62-1.80).

The investigators noted several limitations of their study, including a retrospective design and no information available on recurrence or the duration of endocrine therapy.
 

Why Is Endocrine Therapy So Frequently Omitted in This Patient Group?

Matthew P. Goetz, MD, of the Mayo Clinic, the study’s corresponding author, said in an interview that in Sweden, for example, ER-low patients are explicitly not offered endocrine therapy based on Swedish guidelines.

In other settings, he said, it is unclear what is happening.

“Are patients refusing it? Do physicians not even offer it because they think there is no value? We do not have that granular detail, but our data right now suggests a physician should be having this conversation with patients,” he said.
 

Which ER-Low Patients Are Likely To Benefit?

The findings apply mostly to patients with residual disease after chemotherapy, and underlying biological factors are likely the reason, Dr. Goetz said.

ER-low patients are a heterogeneous group, he explained.

“In genomic profiling, where we look at the underlying biology of these cancers, most of the ER-low cancers are considered the basal subtype of triple negative breast cancer. Those patients should have absolutely zero benefit from endocrine therapy. But there is another group, referred to as the luminal group, which comprises anywhere from 20% to 30% of the ER-low patients.”

Dr. Goetz said he expects to find that this latter group are the patients benefiting from endocrine therapy when they have residual disease.

“We are not yet at the point of saying to patients, ‘you have residual disease after chemotherapy. Let’s check your tumor to see if it is the basal or luminal subtype.’ But that is something that we are planning to look into. What is most important right now is that clinicians be aware of these data, and that there is a suggestion that omitting endocrine therapy may have detrimental effects on survival in this subgroup of patients.”
 

Are the Findings Compelling Enough To Change Clinical Practice Right Away?

In an interview about the findings, Eric Winer, MD, of the Yale Cancer Center in New Haven, Connecticut, cautioned that due to the retrospective study design, “we don’t know how doctors made decisions about who got endocrine therapy and who didn’t.”

The patients with the worst tumors tended not to get endocrine therapy, Dr. Winer noted, and despite attempts to adjust for this, “in any large data set like this, unlike in a randomized trial, you just can’t control for all the bias.”
 

What Should Doctors Tell Patients?

“In the setting of significant side effects from endocrine therapy, we’re still less certain about the benefits of endocrine therapy here than in somebody with an ER-high tumor,” Dr. Winer cautioned.

Nonetheless, he said, the new findings certainly suggest that there may be a benefit for endocrine therapy in patients with ER-low tumors, and doctors should make this known to patients. “It may not be the strongest evidence, but it’s evidence,” he said. “This is very much a question to be raised between the doctor and the patient.”

Dr. Choong and colleagues’ study was funded by a Mayo Clinic Breast Cancer SPORE grant. Dr. Goetz reported consulting fees and research support from pharmaceutical manufacturers, including AstraZeneca, Pfizer, Lilly, and Novartis. Dr. Choong and Dr. Winer reported no financial conflicts of interest.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.

Most younger women diagnosed with nonmetastatic breast cancer will succeed if they attempt to become pregnant after treatment, according to new research.

The findings, presented May 23 in advance of the annual meeting of the American Society of Clinical Oncology (ASCO) represent the most comprehensive look to date at fertility outcomes following treatment for women diagnosed with breast cancer before age 40 (Abstract 1518).

Kimia Sorouri, MD, a research fellow at the Dana-Farber Cancer Center in Boston, Massachusetts, and her colleagues, looked at data from the Young Women’s Breast Cancer study, a multicenter longitudinal cohort study, for 1213 U.S. and Canadian women (74% non-Hispanic white) who were diagnosed with stages 0-III breast cancer between 2006 and 2016. None of the included patients had metastatic disease, prior hysterectomy, or prior oophorectomy at diagnosis.

During a median 11 years of follow up, 197 of the women reported attempting pregnancy. Of these, 73% reported becoming pregnant, and 65% delivered a live infant a median 4 years after cancer diagnosis. The median age at diagnosis was 32 years, and 28% opted for egg or embryo freezing to preserve fertility. Importantly, 68% received chemotherapy, which can impair fertility, with only a small percentage undergoing ovarian suppression during chemotherapy treatment.

Key predictors of pregnancy or live birth in this study were “financial comfort,” a self-reported measure defined as having money left over to spend after bills are paid (odds ratio [OR], 2.04; 95% CI 1.01-4.12; P = .047); younger age at the time of diagnosis; and undergoing fertility preservation interventions at diagnosis (OR, 2.78; 95% CI 1.29-6.00; P = .009). Chemotherapy and other treatment factors were not seen to be associated with pregnancy or birth outcomes.

“Current research that informs our understanding of the impact of breast cancer treatment on pregnancy and live birth rates is fairly limited,” Dr. Sorouri said during an online press conference announcing the findings. Quality data on fertility outcomes has been limited to studies in certain subgroups, such as women with estrogen receptor–positive breast cancers, she noted, while other studies “have short-term follow-up and critically lack prospective assessment of attempt at conception.”

The new findings show, Dr. Sorouri said, “that in this modern cohort with a heightened awareness of fertility, access to fertility preservation can help to mitigate a portion of the damage from chemotherapy and other agents. Importantly, this highlights the need for increased accessibility of fertility preservation services for women newly diagnosed with breast cancer who are interested in a future pregnancy.”

Commenting on Dr. Sorouri and colleagues’ findings, Julie Gralow, MD, a breast cancer researcher and ASCO’s chief medical officer, stressed that, while younger age at diagnosis and financial comfort were two factors outside the scope of clinical oncology practice, “we can impact fertility preservation prior to treatment.”

She called it “critical” that every patient be informed of the impact of a breast cancer diagnosis and treatment on future fertility, and that all young patients interested in future fertility be offered fertility preservation prior to beginning treatment.

Ann Partridge, MD, of Dana-Farber, said in an interview that the findings reflected a decades’ long change in approach. “Twenty years ago when we first started this cohort, people would tell women ‘you can’t get pregnant. It’s too dangerous. You won’t be able to.’ And some indeed aren’t able to, but the majority who are attempting are succeeding, especially if they preserve their eggs or embryos. So even if chemo puts you into menopause or made you subfertile, if you’ve preserved eggs or embryos, we now can mitigate that distressing effect that many cancer patients have suffered from historically. That’s the good news here.”

Nonetheless, Dr. Partridge, an oncologist and the last author of the study, noted, the results reflected success only for women actively attempting pregnancy. “Remember, we’re not including the people who didn’t attempt. There may be some who went into menopause who never banked eggs or embryos, and may never have tried because they went to a doctor who told them they’re not fertile.” Further, she said, not all insurances cover in vitro fertilization for women who have had breast cancer.

The fact that financial comfort was correlated with reproductive success, Dr. Partridge said, speaks to broader issues about access. “It may not be all about insurers. It may be to have the ability, to have the time, the education and the wherewithal to do this right — and about being with doctors who talk about it.”

Dr. Sorouri and colleagues’ study was sponsored by the Breast Cancer Research Foundation and Susan G. Komen. Several co-authors disclosed receiving speaking and/or consulting fees from pharmaceutical companies, and one reported being an employee of GlaxoSmithKline. Dr. Sorouri reported no industry funding, while Dr. Partridge reported research funding from Novartis.

Most younger women diagnosed with nonmetastatic breast cancer will succeed if they attempt to become pregnant after treatment, according to new research.

The findings, presented May 23 in advance of the annual meeting of the American Society of Clinical Oncology (ASCO) represent the most comprehensive look to date at fertility outcomes following treatment for women diagnosed with breast cancer before age 40 (Abstract 1518).

Kimia Sorouri, MD, a research fellow at the Dana-Farber Cancer Center in Boston, Massachusetts, and her colleagues, looked at data from the Young Women’s Breast Cancer study, a multicenter longitudinal cohort study, for 1213 U.S. and Canadian women (74% non-Hispanic white) who were diagnosed with stages 0-III breast cancer between 2006 and 2016. None of the included patients had metastatic disease, prior hysterectomy, or prior oophorectomy at diagnosis.

During a median 11 years of follow up, 197 of the women reported attempting pregnancy. Of these, 73% reported becoming pregnant, and 65% delivered a live infant a median 4 years after cancer diagnosis. The median age at diagnosis was 32 years, and 28% opted for egg or embryo freezing to preserve fertility. Importantly, 68% received chemotherapy, which can impair fertility, with only a small percentage undergoing ovarian suppression during chemotherapy treatment.

Key predictors of pregnancy or live birth in this study were “financial comfort,” a self-reported measure defined as having money left over to spend after bills are paid (odds ratio [OR], 2.04; 95% CI 1.01-4.12; P = .047); younger age at the time of diagnosis; and undergoing fertility preservation interventions at diagnosis (OR, 2.78; 95% CI 1.29-6.00; P = .009). Chemotherapy and other treatment factors were not seen to be associated with pregnancy or birth outcomes.

“Current research that informs our understanding of the impact of breast cancer treatment on pregnancy and live birth rates is fairly limited,” Dr. Sorouri said during an online press conference announcing the findings. Quality data on fertility outcomes has been limited to studies in certain subgroups, such as women with estrogen receptor–positive breast cancers, she noted, while other studies “have short-term follow-up and critically lack prospective assessment of attempt at conception.”

The new findings show, Dr. Sorouri said, “that in this modern cohort with a heightened awareness of fertility, access to fertility preservation can help to mitigate a portion of the damage from chemotherapy and other agents. Importantly, this highlights the need for increased accessibility of fertility preservation services for women newly diagnosed with breast cancer who are interested in a future pregnancy.”

Commenting on Dr. Sorouri and colleagues’ findings, Julie Gralow, MD, a breast cancer researcher and ASCO’s chief medical officer, stressed that, while younger age at diagnosis and financial comfort were two factors outside the scope of clinical oncology practice, “we can impact fertility preservation prior to treatment.”

She called it “critical” that every patient be informed of the impact of a breast cancer diagnosis and treatment on future fertility, and that all young patients interested in future fertility be offered fertility preservation prior to beginning treatment.

Ann Partridge, MD, of Dana-Farber, said in an interview that the findings reflected a decades’ long change in approach. “Twenty years ago when we first started this cohort, people would tell women ‘you can’t get pregnant. It’s too dangerous. You won’t be able to.’ And some indeed aren’t able to, but the majority who are attempting are succeeding, especially if they preserve their eggs or embryos. So even if chemo puts you into menopause or made you subfertile, if you’ve preserved eggs or embryos, we now can mitigate that distressing effect that many cancer patients have suffered from historically. That’s the good news here.”

Nonetheless, Dr. Partridge, an oncologist and the last author of the study, noted, the results reflected success only for women actively attempting pregnancy. “Remember, we’re not including the people who didn’t attempt. There may be some who went into menopause who never banked eggs or embryos, and may never have tried because they went to a doctor who told them they’re not fertile.” Further, she said, not all insurances cover in vitro fertilization for women who have had breast cancer.

The fact that financial comfort was correlated with reproductive success, Dr. Partridge said, speaks to broader issues about access. “It may not be all about insurers. It may be to have the ability, to have the time, the education and the wherewithal to do this right — and about being with doctors who talk about it.”

Dr. Sorouri and colleagues’ study was sponsored by the Breast Cancer Research Foundation and Susan G. Komen. Several co-authors disclosed receiving speaking and/or consulting fees from pharmaceutical companies, and one reported being an employee of GlaxoSmithKline. Dr. Sorouri reported no industry funding, while Dr. Partridge reported research funding from Novartis.

Most younger women diagnosed with nonmetastatic breast cancer will succeed if they attempt to become pregnant after treatment, according to new research.

The findings, presented May 23 in advance of the annual meeting of the American Society of Clinical Oncology (ASCO) represent the most comprehensive look to date at fertility outcomes following treatment for women diagnosed with breast cancer before age 40 (Abstract 1518).

Kimia Sorouri, MD, a research fellow at the Dana-Farber Cancer Center in Boston, Massachusetts, and her colleagues, looked at data from the Young Women’s Breast Cancer study, a multicenter longitudinal cohort study, for 1213 U.S. and Canadian women (74% non-Hispanic white) who were diagnosed with stages 0-III breast cancer between 2006 and 2016. None of the included patients had metastatic disease, prior hysterectomy, or prior oophorectomy at diagnosis.

During a median 11 years of follow up, 197 of the women reported attempting pregnancy. Of these, 73% reported becoming pregnant, and 65% delivered a live infant a median 4 years after cancer diagnosis. The median age at diagnosis was 32 years, and 28% opted for egg or embryo freezing to preserve fertility. Importantly, 68% received chemotherapy, which can impair fertility, with only a small percentage undergoing ovarian suppression during chemotherapy treatment.

Key predictors of pregnancy or live birth in this study were “financial comfort,” a self-reported measure defined as having money left over to spend after bills are paid (odds ratio [OR], 2.04; 95% CI 1.01-4.12; P = .047); younger age at the time of diagnosis; and undergoing fertility preservation interventions at diagnosis (OR, 2.78; 95% CI 1.29-6.00; P = .009). Chemotherapy and other treatment factors were not seen to be associated with pregnancy or birth outcomes.

“Current research that informs our understanding of the impact of breast cancer treatment on pregnancy and live birth rates is fairly limited,” Dr. Sorouri said during an online press conference announcing the findings. Quality data on fertility outcomes has been limited to studies in certain subgroups, such as women with estrogen receptor–positive breast cancers, she noted, while other studies “have short-term follow-up and critically lack prospective assessment of attempt at conception.”

The new findings show, Dr. Sorouri said, “that in this modern cohort with a heightened awareness of fertility, access to fertility preservation can help to mitigate a portion of the damage from chemotherapy and other agents. Importantly, this highlights the need for increased accessibility of fertility preservation services for women newly diagnosed with breast cancer who are interested in a future pregnancy.”

Commenting on Dr. Sorouri and colleagues’ findings, Julie Gralow, MD, a breast cancer researcher and ASCO’s chief medical officer, stressed that, while younger age at diagnosis and financial comfort were two factors outside the scope of clinical oncology practice, “we can impact fertility preservation prior to treatment.”

She called it “critical” that every patient be informed of the impact of a breast cancer diagnosis and treatment on future fertility, and that all young patients interested in future fertility be offered fertility preservation prior to beginning treatment.

Ann Partridge, MD, of Dana-Farber, said in an interview that the findings reflected a decades’ long change in approach. “Twenty years ago when we first started this cohort, people would tell women ‘you can’t get pregnant. It’s too dangerous. You won’t be able to.’ And some indeed aren’t able to, but the majority who are attempting are succeeding, especially if they preserve their eggs or embryos. So even if chemo puts you into menopause or made you subfertile, if you’ve preserved eggs or embryos, we now can mitigate that distressing effect that many cancer patients have suffered from historically. That’s the good news here.”

Nonetheless, Dr. Partridge, an oncologist and the last author of the study, noted, the results reflected success only for women actively attempting pregnancy. “Remember, we’re not including the people who didn’t attempt. There may be some who went into menopause who never banked eggs or embryos, and may never have tried because they went to a doctor who told them they’re not fertile.” Further, she said, not all insurances cover in vitro fertilization for women who have had breast cancer.

The fact that financial comfort was correlated with reproductive success, Dr. Partridge said, speaks to broader issues about access. “It may not be all about insurers. It may be to have the ability, to have the time, the education and the wherewithal to do this right — and about being with doctors who talk about it.”

Dr. Sorouri and colleagues’ study was sponsored by the Breast Cancer Research Foundation and Susan G. Komen. Several co-authors disclosed receiving speaking and/or consulting fees from pharmaceutical companies, and one reported being an employee of GlaxoSmithKline. Dr. Sorouri reported no industry funding, while Dr. Partridge reported research funding from Novartis.

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article first appeared on Medscape.com.

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article first appeared on Medscape.com.

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article first appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.