Breast Cancer

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.

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

Nearly one in three physicians endorsing drugs and devices on the social media platform X did not disclose that they received payments from the manufacturers, according to a new study published in JAMA.

Lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, told this news organization that he and his colleagues undertook the study in part to see whether physicians were adhering to professional and industry guidelines regarding marketing communications.

The team reviewed posts by physicians on X during 2022, looking for key words that might indicate that the posts were intended as endorsements of a product. The researchers then delved into the Centers for Medicare and Medicaid Services Open Payments database to see how many of those identified as having endorsed a product were paid by the manufacturers.

What Dr. Mitchell found concerned him, he said.

Overall, the researchers identified 28 physician endorsers who received a total of $1.4 million from sponsors in 2022. Among these, 26 physicians (93%) received payments from the product’s manufacturer, totaling $713,976, and 24 physicians (86%) accepted payments related to the endorsed drug or device, totaling $492,098.

While most did disclose that the posts were sponsored — by adding the word “sponsored” or using #sponsored — nine physicians did not.

Although 28 physician endorsers represent a “small fraction” of the overall number of physicians who use X, each endorsement was ultimately posted dozens, if not hundreds of times, said Dr. Mitchell. In fact, he said he saw the same particular endorsement post every time he opened his X app for months.

Overall, Dr. Mitchell noted that it’s less about the fact that the endorsements are occurring on social media and more that there are these paid endorsements taking place at all.

Among the physician specialties promoting a product, urologists and oncologists dominated. Almost one third were urologists, and 57% were oncologists — six medical oncologists, six radiation oncologists, and four gynecologic oncologists. Of the remaining three physicians, two were internists and one was a pulmonary and critical care medicine specialist.

The authors tracked posts from physicians and industry accounts. Many of the posts on industry accounts were physician testimonials, usually videos. Almost half — 8 of 17 — of those testimonials did not disclose that the doctor was being paid by the manufacturer. In another case, a physician did not disclose that they were paid to endorse a white paper.

Fifteen promotional posts were for a Boston Scientific product, followed by six for GlaxoSmithKline, two for Eisai, two for Exelixis, and one each for AstraZeneca, Novartis, and Pfizer.

In general, Dr. Mitchell said, industry guidelines suggest that manufacturer-paid speakers or consultants should have well-regarded expertise in the area they are being asked to weigh in on, but most physician endorsers in the study were not key opinion leaders or experts.

The authors examined the paid endorsers’ H-index — a measure of academic productivity provided by Scopus. Overall, 19 of the 28 physicians had an H-index below 20, which is considered less accomplished, and 14 had no published research related to the endorsed product.

Ten received payments from manufacturers for research purposes, and only one received research payments related to the endorsed product ($224,577).

“Physicians’ participation in industry marketing raises questions regarding professionalism and their responsibilities as patient advocates,” the JAMA authors wrote.

The study was supported by grants from the National Cancer Institute. Dr. Mitchell reported no relevant financial relationships. Coauthors Samer Al Hadidi, MD, reported receiving personal fees from Pfizer, Sanofi, and Janssen during the conduct of the study, and Timothy S. Anderson, MD, reported receiving grants from the National Institute on Aging, the American Heart Association, and the American College of Cardiology, and receiving consulting fees from the American Medical Student Association. Dr. Anderson is also an associate editor of JAMA Internal Medicine.

A version of this article appeared on Medscape.com.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article appeared on Medscape.com.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article appeared on Medscape.com.

CHICAGO — Carlos, a 21-year-old, lay in a hospital bed, barely clinging to life. Following a stem cell transplant for leukemia, Carlos had developed a life-threatening case of graft-vs-host disease.

But Carlos’ mother had faith.

“I have hope things will get better,” she said, via interpreter, to Richard Leiter, MD, a palliative care doctor in training at that time.

“I hope they will,” Dr. Leiter told her.

“I should have stopped there,” said Dr. Leiter, recounting an early-career lesson on hope during the ASCO Voices session at the American Society of Clinical Oncology annual meeting. “But in my eagerness to show my attending and myself that I could handle this conversation, I kept going, mistakenly.”

“But none of us think they will,” Dr. Leiter continued.

Carlos’ mother looked Dr. Leiter in the eye. “You want him to die,” she said.

“I knew, even then, that she was right,” recalled Dr. Leiter, now a palliative care physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, Boston.

Although there was nothing he could do to save Carlos, Dr. Leiter also couldn’t sit with the extreme suffering. “The pain was too great,” Dr. Leiter said. “I needed her to adopt our narrative that we had done everything we could to help him live, and now, we would do everything we could to help his death be a comfortable one.”

But looking back, Dr. Leiter realized, “How could we have asked her to accept what was fundamentally unacceptable, to comprehend the incomprehensible?”
 

The Importance of Hope

Hope is not only a feature of human cognition but also a measurable and malleable construct that can affect life outcomes, Alan B. Astrow, MD, said during an ASCO symposium on “The Art and Science of Hope.”

“How we think about hope directly influences patient care,” said Dr. Astrow, chief of hematology and medical oncology at NewYork-Presbyterian Brooklyn Methodist Hospital and a professor of clinical medicine at Weill Cornell Medicine in New York City.

Hope, whatever it turns out to be neurobiologically, is “very much a gift” that underlies human existence, he said.

Physicians have the capacity to restore or shatter a patient’s hopes, and those who come to understand the importance of hope will wish to extend the gift to others, Dr. Astrow said.

Asking patients about their hopes is the “golden question,” Steven Z. Pantilat, MD, said at the symposium. “When you think about the future, what do you hope for?”

Often, the answers reveal not only “things beyond a cure that matter tremendously to the patient but things that we can help with,” said Dr. Pantilat, professor and chief of the Division of Palliative Medicine at the University of California San Francisco.

Dr. Pantilat recalled a patient with advanced pancreatic cancer who wished to see her daughter’s wedding in 10 months. He knew that was unlikely, but the discussion led to another solution.

Her daughter moved the wedding to the ICU.

Hope can persist and uplift even in the darkest of times, and “as clinicians, we need to be in the true hope business,” he said.

While some patients may wish for a cure, others may want more time with family or comfort in the face of suffering. People can “hope for all the things that can still be, despite the fact that there’s a lot of things that can’t,” he said.

However, fear that a patient will hope for a cure, and that the difficult discussions to follow might destroy hope or lead to false hope, sometimes means physicians won’t begin the conversation.

“We want to be honest with our patients — compassionate and kind, but honest — when we talk about their hopes,” Dr. Pantilat explained. Sometimes that means he needs to tell patients, “I wish that could happen. I wish I had a treatment that could make your cancer go away, but unfortunately, I don’t. So let’s think about what else we can do to help you.”

Having these difficult discussions matters. The evidence, although limited, indicates that feeling hopeful can improve patients’ well-being and may even boost their cancer outcomes.

One recent study found, for instance, that patients who reported feeling more hopeful also had lower levels of depression and anxiety. Early research also suggests that greater levels of hope may have a hand in reducing inflammation in patients with ovarian cancer and could even improve survival in some patients with advanced cancer.

For Dr. Leiter, while these lessons came early in his career as a palliative care physician, they persist and influence his practice today.

“I know that I could not have prevented Carlos’ death. None of us could have, and none of us could have protected his mother from the unimaginable grief that will stay with her for the rest of her life,” he said. “But I could have made things just a little bit less difficult for her.

“I could have acted as her guide rather than her cross-examiner,” he continued, explaining that he now sees hope as “a generous collaborator” that can coexist with rising creatinine levels, failing livers, and fears about intubation.

“As clinicians, we can always find space to hope with our patients and their families,” he said. “So now, years later when I sit with a terrified and grieving family and they tell me they hope their loved one gets better, I remember Carlos’ mother’s eyes piercing mine ... and I know how to respond: ‘I hope so, too.’ And I do.”
 

A version of this article 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.

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 US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.

Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time. 

“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”

Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.

In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.

Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.

At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).

However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.

After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.

Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production. 

Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.

“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”

“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”

Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.

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

BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.

Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time. 

“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”

Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.

In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.

Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.

At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).

However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.

After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.

Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production. 

Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.

“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”

“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”

Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.

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

BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.

Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time. 

“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”

Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.

In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.

Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.

At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).

However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.

After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.

Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production. 

Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.

“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”

“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”

Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.

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.