Breast Cancer

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.

Triple-negative breast cancer (TNBC) is characterized by the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) expression. Historically, treatments targeting HER2 were found to be ineffective in patients with TNBC and known HER2-zero status. Researchers more recently identified a new type of TNBC involving patients with low expression of HER2. Patients with this type of breast cancer, now referred to as HER2-low, have immunohistochemical (IHC) analysis scores of 1+ or 2+ and negative in situ hybridization (ISH) stain.

In a new study, patients with TNBC who initially tested as having HER2-zero status were later found to have HER2-low status following repeated biopsies. These HER2-low results were of great clinical significance for this patient population, said Yael Bar, MD, PhD, during her presentation of the research, at the annual meeting of the American Society of Clinical Oncology (ASCO).

Previously, the DESTINY-Breast04 trial demonstrated that the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) for patients with HER2-low metastatic breast cancer. “As a result [of the DESTINY-Breast04 findings], T-DXd is now approved for HER2-low but not HER2-zero triple-negative metastatic breast cancer."

“While HER2-low is detected in about 30%-50% of patients with triple-negative breast cancer, several studies have shown that HER2 status is heterogeneous and also dynamic over time, said Dr. Bar, who is an international research fellow in the breast cancer group at Mass General Cancer Center, Boston.

In the new study, Dr. Bar and her co-authors retrospectively identified 512 TNBC patients from 2000 to 2022 from an institutional database. They included core, surgical, or metastatic biopsies. Participants had a mean age of 52 years, with 54% over age 50. They were 83% White, 7% African American, 5% Asian, 3% Hispanic, and 2% other. Stage II was most common at diagnosis at 48%, followed by stage 1 (28%), stage 3 (14%), and stage IV (8%).

Most patients had undergone one (38%) or two (45%) biopsies, while 9% underwent three biopsies, 6% underwent four biopsies, and 2% underwent five or more.

Among all 512 patients in the study, 60% had a HER2-low result on their first biopsy. As of the second biopsy, 73% had at least one HER2-low result, with 13% of the first HER2-low results occurring at the second biopsy. As of the third biopsy, 81% had a HER2-low result, with 9% occurring for the first time. At the fourth biopsy, 86% had a positive result, with 8% occurring for the first time. All patients with five or more biopsies had at least one HER2-low result and none were first-time results.

At the second biopsy, a HER2-low result was detected for 32% of patients for the first time. At the third biopsy, a new HER2-low result was detected in 33%, and at the fourth biopsy, a new HER-2 result was detected in 38%.

The researchers matched early and metastatic biopsies in 71 patients, and 44% had changed status: 68% of those with a status change went HER2-low to HER2-zero, 26% from HER2-zero to HER2-low, and 6% from HER2-low to HER2-positive. Among 50 patients with matched metastatic biopsies, 33% had a change in status, with 63% going from HER2-zero to HER2-low, 31% from HER2-low to HER2-zero, and 6% from HER2-low to HER2-positive.

“We showed here that repeat biopsies can identify new HER2-low results for patients who were previously ineligible for T-DXd; and therefore, we think that a repeat biopsy could be considered if feasible and safe. Also, if a repeat biopsy is performed for any reason, but mainly upon metastatic recurrence, receptors should be retested,” said Dr. Bar.

After Dr. Bar’s presentation, Barbara Pistilli, MD served as a discussant. She noted the increased HER2-low results over successive biopsies. “However, here the question is, are these results related to the changes in the analytical methods over the past 20 years or the changes in the guidelines in terms of definition of HER2 status, or are they more related to a true evolution of HER2 status with the evolution of the disease?” she said during her presentation. Dr. Pistilli is chair of the breast disease committee at Gustave Roussy in Villejuif, France.

She also said that HER2 expression can vary even between different parts of the same tumor and called for alternative methods to following HER2 expression. “I don’t think that we can follow our patients with multiple biopsies over the disease evolution, so we have to find other tools, such as target-positive [circulating tumor cells], or antibody-radiolabeled PET scan in order to better follow the intermetastasis target heterogeneity over time, and finally define what is the optimal ADC sequential strategy for each patient,” said Dr. Pistilli.

Comoderator Michael Danso, MD, also weighed in when asked for comment. 

“It was an important trial to show that serial biopsies potentially allow more patients to receive trastuzumab deruxtecan,” said Dr. Danso, who is the research director at Virginia Oncology Associates, Norfolk. However, he pointed out the concerns of a statistician who had spoken up during the question-and-answer session who said that the positive results could simply be the consequence of repeated testing. “If you do a test often enough, statistically you’re going to get a difference in outcome. That was an important point made. Also, if you’re going to get 100% of patients who are eventually going to [develop HER2-low status], the question is, can you just treat everybody with trastuzumab deruxtecan and not do these sequential biopsies? Obviously that is subject to cost; it’s subject to toxicity as well, so you probably want documentation that there is a HER2-low result,” said Dr. Danso.

Dr. Bar has no relevant financial disclosures. Dr. Pistilli has consulted for or advised AstraZeneca, Daiichi Sankyo/UCB Japan, Myriad Genetics, Novartis, PIERRE FABRE, and Puma Biotechnology. She has received research funding through her institution from AstraZeneca, Daiichi Sankyo, Gilead Sciences, Merus, Pfizer, and Puma Biotechnology. She has received travel or accommodation expenses from AstraZeneca, Daiichi Sankyo Europe, MSD Oncology, Novartis, Pfizer, and Pierre Fabre. Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen.

*This story was updated on 6/13/2023.

Triple-negative breast cancer (TNBC) is characterized by the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) expression. Historically, treatments targeting HER2 were found to be ineffective in patients with TNBC and known HER2-zero status. Researchers more recently identified a new type of TNBC involving patients with low expression of HER2. Patients with this type of breast cancer, now referred to as HER2-low, have immunohistochemical (IHC) analysis scores of 1+ or 2+ and negative in situ hybridization (ISH) stain.

In a new study, patients with TNBC who initially tested as having HER2-zero status were later found to have HER2-low status following repeated biopsies. These HER2-low results were of great clinical significance for this patient population, said Yael Bar, MD, PhD, during her presentation of the research, at the annual meeting of the American Society of Clinical Oncology (ASCO).

Previously, the DESTINY-Breast04 trial demonstrated that the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) for patients with HER2-low metastatic breast cancer. “As a result [of the DESTINY-Breast04 findings], T-DXd is now approved for HER2-low but not HER2-zero triple-negative metastatic breast cancer."

“While HER2-low is detected in about 30%-50% of patients with triple-negative breast cancer, several studies have shown that HER2 status is heterogeneous and also dynamic over time, said Dr. Bar, who is an international research fellow in the breast cancer group at Mass General Cancer Center, Boston.

In the new study, Dr. Bar and her co-authors retrospectively identified 512 TNBC patients from 2000 to 2022 from an institutional database. They included core, surgical, or metastatic biopsies. Participants had a mean age of 52 years, with 54% over age 50. They were 83% White, 7% African American, 5% Asian, 3% Hispanic, and 2% other. Stage II was most common at diagnosis at 48%, followed by stage 1 (28%), stage 3 (14%), and stage IV (8%).

Most patients had undergone one (38%) or two (45%) biopsies, while 9% underwent three biopsies, 6% underwent four biopsies, and 2% underwent five or more.

Among all 512 patients in the study, 60% had a HER2-low result on their first biopsy. As of the second biopsy, 73% had at least one HER2-low result, with 13% of the first HER2-low results occurring at the second biopsy. As of the third biopsy, 81% had a HER2-low result, with 9% occurring for the first time. At the fourth biopsy, 86% had a positive result, with 8% occurring for the first time. All patients with five or more biopsies had at least one HER2-low result and none were first-time results.

At the second biopsy, a HER2-low result was detected for 32% of patients for the first time. At the third biopsy, a new HER2-low result was detected in 33%, and at the fourth biopsy, a new HER-2 result was detected in 38%.

The researchers matched early and metastatic biopsies in 71 patients, and 44% had changed status: 68% of those with a status change went HER2-low to HER2-zero, 26% from HER2-zero to HER2-low, and 6% from HER2-low to HER2-positive. Among 50 patients with matched metastatic biopsies, 33% had a change in status, with 63% going from HER2-zero to HER2-low, 31% from HER2-low to HER2-zero, and 6% from HER2-low to HER2-positive.

“We showed here that repeat biopsies can identify new HER2-low results for patients who were previously ineligible for T-DXd; and therefore, we think that a repeat biopsy could be considered if feasible and safe. Also, if a repeat biopsy is performed for any reason, but mainly upon metastatic recurrence, receptors should be retested,” said Dr. Bar.

After Dr. Bar’s presentation, Barbara Pistilli, MD served as a discussant. She noted the increased HER2-low results over successive biopsies. “However, here the question is, are these results related to the changes in the analytical methods over the past 20 years or the changes in the guidelines in terms of definition of HER2 status, or are they more related to a true evolution of HER2 status with the evolution of the disease?” she said during her presentation. Dr. Pistilli is chair of the breast disease committee at Gustave Roussy in Villejuif, France.

She also said that HER2 expression can vary even between different parts of the same tumor and called for alternative methods to following HER2 expression. “I don’t think that we can follow our patients with multiple biopsies over the disease evolution, so we have to find other tools, such as target-positive [circulating tumor cells], or antibody-radiolabeled PET scan in order to better follow the intermetastasis target heterogeneity over time, and finally define what is the optimal ADC sequential strategy for each patient,” said Dr. Pistilli.

Comoderator Michael Danso, MD, also weighed in when asked for comment. 

“It was an important trial to show that serial biopsies potentially allow more patients to receive trastuzumab deruxtecan,” said Dr. Danso, who is the research director at Virginia Oncology Associates, Norfolk. However, he pointed out the concerns of a statistician who had spoken up during the question-and-answer session who said that the positive results could simply be the consequence of repeated testing. “If you do a test often enough, statistically you’re going to get a difference in outcome. That was an important point made. Also, if you’re going to get 100% of patients who are eventually going to [develop HER2-low status], the question is, can you just treat everybody with trastuzumab deruxtecan and not do these sequential biopsies? Obviously that is subject to cost; it’s subject to toxicity as well, so you probably want documentation that there is a HER2-low result,” said Dr. Danso.

Dr. Bar has no relevant financial disclosures. Dr. Pistilli has consulted for or advised AstraZeneca, Daiichi Sankyo/UCB Japan, Myriad Genetics, Novartis, PIERRE FABRE, and Puma Biotechnology. She has received research funding through her institution from AstraZeneca, Daiichi Sankyo, Gilead Sciences, Merus, Pfizer, and Puma Biotechnology. She has received travel or accommodation expenses from AstraZeneca, Daiichi Sankyo Europe, MSD Oncology, Novartis, Pfizer, and Pierre Fabre. Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen.

*This story was updated on 6/13/2023.

Triple-negative breast cancer (TNBC) is characterized by the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) expression. Historically, treatments targeting HER2 were found to be ineffective in patients with TNBC and known HER2-zero status. Researchers more recently identified a new type of TNBC involving patients with low expression of HER2. Patients with this type of breast cancer, now referred to as HER2-low, have immunohistochemical (IHC) analysis scores of 1+ or 2+ and negative in situ hybridization (ISH) stain.

In a new study, patients with TNBC who initially tested as having HER2-zero status were later found to have HER2-low status following repeated biopsies. These HER2-low results were of great clinical significance for this patient population, said Yael Bar, MD, PhD, during her presentation of the research, at the annual meeting of the American Society of Clinical Oncology (ASCO).

Previously, the DESTINY-Breast04 trial demonstrated that the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) for patients with HER2-low metastatic breast cancer. “As a result [of the DESTINY-Breast04 findings], T-DXd is now approved for HER2-low but not HER2-zero triple-negative metastatic breast cancer."

“While HER2-low is detected in about 30%-50% of patients with triple-negative breast cancer, several studies have shown that HER2 status is heterogeneous and also dynamic over time, said Dr. Bar, who is an international research fellow in the breast cancer group at Mass General Cancer Center, Boston.

In the new study, Dr. Bar and her co-authors retrospectively identified 512 TNBC patients from 2000 to 2022 from an institutional database. They included core, surgical, or metastatic biopsies. Participants had a mean age of 52 years, with 54% over age 50. They were 83% White, 7% African American, 5% Asian, 3% Hispanic, and 2% other. Stage II was most common at diagnosis at 48%, followed by stage 1 (28%), stage 3 (14%), and stage IV (8%).

Most patients had undergone one (38%) or two (45%) biopsies, while 9% underwent three biopsies, 6% underwent four biopsies, and 2% underwent five or more.

Among all 512 patients in the study, 60% had a HER2-low result on their first biopsy. As of the second biopsy, 73% had at least one HER2-low result, with 13% of the first HER2-low results occurring at the second biopsy. As of the third biopsy, 81% had a HER2-low result, with 9% occurring for the first time. At the fourth biopsy, 86% had a positive result, with 8% occurring for the first time. All patients with five or more biopsies had at least one HER2-low result and none were first-time results.

At the second biopsy, a HER2-low result was detected for 32% of patients for the first time. At the third biopsy, a new HER2-low result was detected in 33%, and at the fourth biopsy, a new HER-2 result was detected in 38%.

The researchers matched early and metastatic biopsies in 71 patients, and 44% had changed status: 68% of those with a status change went HER2-low to HER2-zero, 26% from HER2-zero to HER2-low, and 6% from HER2-low to HER2-positive. Among 50 patients with matched metastatic biopsies, 33% had a change in status, with 63% going from HER2-zero to HER2-low, 31% from HER2-low to HER2-zero, and 6% from HER2-low to HER2-positive.

“We showed here that repeat biopsies can identify new HER2-low results for patients who were previously ineligible for T-DXd; and therefore, we think that a repeat biopsy could be considered if feasible and safe. Also, if a repeat biopsy is performed for any reason, but mainly upon metastatic recurrence, receptors should be retested,” said Dr. Bar.

After Dr. Bar’s presentation, Barbara Pistilli, MD served as a discussant. She noted the increased HER2-low results over successive biopsies. “However, here the question is, are these results related to the changes in the analytical methods over the past 20 years or the changes in the guidelines in terms of definition of HER2 status, or are they more related to a true evolution of HER2 status with the evolution of the disease?” she said during her presentation. Dr. Pistilli is chair of the breast disease committee at Gustave Roussy in Villejuif, France.

She also said that HER2 expression can vary even between different parts of the same tumor and called for alternative methods to following HER2 expression. “I don’t think that we can follow our patients with multiple biopsies over the disease evolution, so we have to find other tools, such as target-positive [circulating tumor cells], or antibody-radiolabeled PET scan in order to better follow the intermetastasis target heterogeneity over time, and finally define what is the optimal ADC sequential strategy for each patient,” said Dr. Pistilli.

Comoderator Michael Danso, MD, also weighed in when asked for comment. 

“It was an important trial to show that serial biopsies potentially allow more patients to receive trastuzumab deruxtecan,” said Dr. Danso, who is the research director at Virginia Oncology Associates, Norfolk. However, he pointed out the concerns of a statistician who had spoken up during the question-and-answer session who said that the positive results could simply be the consequence of repeated testing. “If you do a test often enough, statistically you’re going to get a difference in outcome. That was an important point made. Also, if you’re going to get 100% of patients who are eventually going to [develop HER2-low status], the question is, can you just treat everybody with trastuzumab deruxtecan and not do these sequential biopsies? Obviously that is subject to cost; it’s subject to toxicity as well, so you probably want documentation that there is a HER2-low result,” said Dr. Danso.

Dr. Bar has no relevant financial disclosures. Dr. Pistilli has consulted for or advised AstraZeneca, Daiichi Sankyo/UCB Japan, Myriad Genetics, Novartis, PIERRE FABRE, and Puma Biotechnology. She has received research funding through her institution from AstraZeneca, Daiichi Sankyo, Gilead Sciences, Merus, Pfizer, and Puma Biotechnology. She has received travel or accommodation expenses from AstraZeneca, Daiichi Sankyo Europe, MSD Oncology, Novartis, Pfizer, and Pierre Fabre. Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen.

*This story was updated on 6/13/2023.

CHICAGO – Nearly 60% of health care providers surveyed failed to choose the same treatment strategies for HER2– early breast cancer as a panel of five oncologists with expertise in breast cancer, a new study finds.

The discrepancy suggests that many providers aren’t aware of the findings of recent landmark trials that formed the basis of the panel’s opinions, said study coauthor Denise A. Yardley, MD, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville, in an interview. The findings, based on responses to a treatment decision tool, were presented in a poster at the annual meeting of the American Society of Clinical Oncology.

Study methods and results

For the new study, researchers analyzed how 547 providers – and the panel – responded to 10 case scenarios in high-risk HER2– early breast cancer between June 2022 and January 2023.

Among the providers surveyed, 72% identified as physicians, including oncologists, hematologists/oncologists, surgery oncologists, radiation oncologists, and pathologists. One percent said they were nurse practitioners or physician assistants, 7% said they were pharmacists, 1% were nurses, and the specific roles of the remaining 19% were unknown, but included medical students, according to Dr. Yardley, who is a breast cancer oncologist.

The study authors developed the free decision tool – available via the medical education company Clinical Care Options – to help oncologists navigate new treatment options for high-risk HER2– early breast cancer. The Food and Drug Administration has recently approved drugs such as abemaciclib, olaparib, and pembrolizumab for the condition.

Health care providers enter details into the tool about their patients along with their intended treatment plans. The tool then shows them recommendations for treatment from a panel of five oncologists with expertise in oncology. The members of the panel based their perspectives on the findings of the KEYNOTE-522 (pembrolizumab), OlympiA (olaparib), and monarchE (abemaciclib) trials.

The oncologists with expertise in breast cancer, who provided recommendations in March 2022, generally agreed about the best treatments, Dr. Yardley said.

The other health care providers surveyed didn’t agree with the breast cancer experts about the best treatment 58.8% of the time.

For example, one scenario describes a HR+, HER2– patient with no deleterious BRCA mutation – or unknown status – who fits the monarchE high-risk criteria. All the breast cancer experts on the panel recommended abemaciclib and endocrine therapy. But 203 providers supported a variety of strategies: endocrine therapy alone (9%), chemotherapy followed by endocrine therapy (49%), and olaparib and endocrine therapy (2%). Only 37% opted for abemaciclib and endocrine therapy, and 4% were uncertain.

Another scenario describes a patient with triple-negative breast cancer with no residual disease after neoadjuvant chemotherapy. All the experts agreed on a strategy of no adjuvant therapy plus observation. Forty percent of 25 providers agreed with this approach, but 24% were uncertain, 12% chose pembrolizumab, and 24% chose capecitabine.

In many cases, providers chose more intensive treatment options than the experts did, Dr. Yardley said.

Overtreatment in cancer is often a reflex for oncologists, she said, although “we’re learning to deescalate these treatment algorithms where there is really no benefit [to extra treatment].”

“It’s a challenge for some of these oncologists who are busy and dealing with multiple solid tumor types to keep up with the nuances of a rapidly changing field,” Dr. Yardley noted.

Many community oncologists aren’t specialists in one type of cancer and must try to keep up with treatment recommendations regarding multiple types, she continued.
 

Decision tool’s value explained

According to the study, 32% of providers changed their treatment choices in clinical practice after they learned about the expert perspectives via the decision tool; 46% said the expert opinions confirmed that their choices were best practice.

The value of the tool is its ability to help providers make better decisions about patient care, Dr. Yardley said. “There seems to be a need for this kind of support.”

In an interview, University of Pittsburgh Medical Center oncologist Adam M. Brufsky, MD, PhD – who wasn’t involved with the study – said he was surprised by the amount of disagreement between the expert and provider perspectives on treatment. However, he noted that community oncologists – unlike the breast cancer experts – often don’t see just one type of cancer.

“You just have to know so much now as an oncologist,” Dr. Brufsky said. He recommended that colleagues take advantage of decision support tools, such as cancer treatment pathways.

The study was funded by AstraZeneca, Lilly, and Merck Sharp & Dohme. Dr. Yardley has no disclosures, and disclosure information from other authors was not available. Dr. Brufsky discloses consulting support from AstraZeneca, Lilly, and Merck and grants from AstraZeneca.

CHICAGO – Nearly 60% of health care providers surveyed failed to choose the same treatment strategies for HER2– early breast cancer as a panel of five oncologists with expertise in breast cancer, a new study finds.

The discrepancy suggests that many providers aren’t aware of the findings of recent landmark trials that formed the basis of the panel’s opinions, said study coauthor Denise A. Yardley, MD, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville, in an interview. The findings, based on responses to a treatment decision tool, were presented in a poster at the annual meeting of the American Society of Clinical Oncology.

Study methods and results

For the new study, researchers analyzed how 547 providers – and the panel – responded to 10 case scenarios in high-risk HER2– early breast cancer between June 2022 and January 2023.

Among the providers surveyed, 72% identified as physicians, including oncologists, hematologists/oncologists, surgery oncologists, radiation oncologists, and pathologists. One percent said they were nurse practitioners or physician assistants, 7% said they were pharmacists, 1% were nurses, and the specific roles of the remaining 19% were unknown, but included medical students, according to Dr. Yardley, who is a breast cancer oncologist.

The study authors developed the free decision tool – available via the medical education company Clinical Care Options – to help oncologists navigate new treatment options for high-risk HER2– early breast cancer. The Food and Drug Administration has recently approved drugs such as abemaciclib, olaparib, and pembrolizumab for the condition.

Health care providers enter details into the tool about their patients along with their intended treatment plans. The tool then shows them recommendations for treatment from a panel of five oncologists with expertise in oncology. The members of the panel based their perspectives on the findings of the KEYNOTE-522 (pembrolizumab), OlympiA (olaparib), and monarchE (abemaciclib) trials.

The oncologists with expertise in breast cancer, who provided recommendations in March 2022, generally agreed about the best treatments, Dr. Yardley said.

The other health care providers surveyed didn’t agree with the breast cancer experts about the best treatment 58.8% of the time.

For example, one scenario describes a HR+, HER2– patient with no deleterious BRCA mutation – or unknown status – who fits the monarchE high-risk criteria. All the breast cancer experts on the panel recommended abemaciclib and endocrine therapy. But 203 providers supported a variety of strategies: endocrine therapy alone (9%), chemotherapy followed by endocrine therapy (49%), and olaparib and endocrine therapy (2%). Only 37% opted for abemaciclib and endocrine therapy, and 4% were uncertain.

Another scenario describes a patient with triple-negative breast cancer with no residual disease after neoadjuvant chemotherapy. All the experts agreed on a strategy of no adjuvant therapy plus observation. Forty percent of 25 providers agreed with this approach, but 24% were uncertain, 12% chose pembrolizumab, and 24% chose capecitabine.

In many cases, providers chose more intensive treatment options than the experts did, Dr. Yardley said.

Overtreatment in cancer is often a reflex for oncologists, she said, although “we’re learning to deescalate these treatment algorithms where there is really no benefit [to extra treatment].”

“It’s a challenge for some of these oncologists who are busy and dealing with multiple solid tumor types to keep up with the nuances of a rapidly changing field,” Dr. Yardley noted.

Many community oncologists aren’t specialists in one type of cancer and must try to keep up with treatment recommendations regarding multiple types, she continued.
 

Decision tool’s value explained

According to the study, 32% of providers changed their treatment choices in clinical practice after they learned about the expert perspectives via the decision tool; 46% said the expert opinions confirmed that their choices were best practice.

The value of the tool is its ability to help providers make better decisions about patient care, Dr. Yardley said. “There seems to be a need for this kind of support.”

In an interview, University of Pittsburgh Medical Center oncologist Adam M. Brufsky, MD, PhD – who wasn’t involved with the study – said he was surprised by the amount of disagreement between the expert and provider perspectives on treatment. However, he noted that community oncologists – unlike the breast cancer experts – often don’t see just one type of cancer.

“You just have to know so much now as an oncologist,” Dr. Brufsky said. He recommended that colleagues take advantage of decision support tools, such as cancer treatment pathways.

The study was funded by AstraZeneca, Lilly, and Merck Sharp & Dohme. Dr. Yardley has no disclosures, and disclosure information from other authors was not available. Dr. Brufsky discloses consulting support from AstraZeneca, Lilly, and Merck and grants from AstraZeneca.

CHICAGO – Nearly 60% of health care providers surveyed failed to choose the same treatment strategies for HER2– early breast cancer as a panel of five oncologists with expertise in breast cancer, a new study finds.

The discrepancy suggests that many providers aren’t aware of the findings of recent landmark trials that formed the basis of the panel’s opinions, said study coauthor Denise A. Yardley, MD, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville, in an interview. The findings, based on responses to a treatment decision tool, were presented in a poster at the annual meeting of the American Society of Clinical Oncology.

Study methods and results

For the new study, researchers analyzed how 547 providers – and the panel – responded to 10 case scenarios in high-risk HER2– early breast cancer between June 2022 and January 2023.

Among the providers surveyed, 72% identified as physicians, including oncologists, hematologists/oncologists, surgery oncologists, radiation oncologists, and pathologists. One percent said they were nurse practitioners or physician assistants, 7% said they were pharmacists, 1% were nurses, and the specific roles of the remaining 19% were unknown, but included medical students, according to Dr. Yardley, who is a breast cancer oncologist.

The study authors developed the free decision tool – available via the medical education company Clinical Care Options – to help oncologists navigate new treatment options for high-risk HER2– early breast cancer. The Food and Drug Administration has recently approved drugs such as abemaciclib, olaparib, and pembrolizumab for the condition.

Health care providers enter details into the tool about their patients along with their intended treatment plans. The tool then shows them recommendations for treatment from a panel of five oncologists with expertise in oncology. The members of the panel based their perspectives on the findings of the KEYNOTE-522 (pembrolizumab), OlympiA (olaparib), and monarchE (abemaciclib) trials.

The oncologists with expertise in breast cancer, who provided recommendations in March 2022, generally agreed about the best treatments, Dr. Yardley said.

The other health care providers surveyed didn’t agree with the breast cancer experts about the best treatment 58.8% of the time.

For example, one scenario describes a HR+, HER2– patient with no deleterious BRCA mutation – or unknown status – who fits the monarchE high-risk criteria. All the breast cancer experts on the panel recommended abemaciclib and endocrine therapy. But 203 providers supported a variety of strategies: endocrine therapy alone (9%), chemotherapy followed by endocrine therapy (49%), and olaparib and endocrine therapy (2%). Only 37% opted for abemaciclib and endocrine therapy, and 4% were uncertain.

Another scenario describes a patient with triple-negative breast cancer with no residual disease after neoadjuvant chemotherapy. All the experts agreed on a strategy of no adjuvant therapy plus observation. Forty percent of 25 providers agreed with this approach, but 24% were uncertain, 12% chose pembrolizumab, and 24% chose capecitabine.

In many cases, providers chose more intensive treatment options than the experts did, Dr. Yardley said.

Overtreatment in cancer is often a reflex for oncologists, she said, although “we’re learning to deescalate these treatment algorithms where there is really no benefit [to extra treatment].”

“It’s a challenge for some of these oncologists who are busy and dealing with multiple solid tumor types to keep up with the nuances of a rapidly changing field,” Dr. Yardley noted.

Many community oncologists aren’t specialists in one type of cancer and must try to keep up with treatment recommendations regarding multiple types, she continued.
 

Decision tool’s value explained

According to the study, 32% of providers changed their treatment choices in clinical practice after they learned about the expert perspectives via the decision tool; 46% said the expert opinions confirmed that their choices were best practice.

The value of the tool is its ability to help providers make better decisions about patient care, Dr. Yardley said. “There seems to be a need for this kind of support.”

In an interview, University of Pittsburgh Medical Center oncologist Adam M. Brufsky, MD, PhD – who wasn’t involved with the study – said he was surprised by the amount of disagreement between the expert and provider perspectives on treatment. However, he noted that community oncologists – unlike the breast cancer experts – often don’t see just one type of cancer.

“You just have to know so much now as an oncologist,” Dr. Brufsky said. He recommended that colleagues take advantage of decision support tools, such as cancer treatment pathways.

The study was funded by AstraZeneca, Lilly, and Merck Sharp & Dohme. Dr. Yardley has no disclosures, and disclosure information from other authors was not available. Dr. Brufsky discloses consulting support from AstraZeneca, Lilly, and Merck and grants from AstraZeneca.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

CHICAGO – Patients with advanced estrogen receptor–positive, HER-negative breast cancer receiving first line treatment with CDK4/6 inhibitors (CDK4/6i) experienced no progression-free survival (PFS) or overall survival (OS) advantages over those who received the same therapy as second line treatment.

That was the conclusion of the phase 3 SONIA study, which was presented at the annual meeting of the American Society of Clinical Oncology.

The benefit from first line therapy is not maintained and almost completely disappears when patients in the control arm cross over to receive CDK4/6 inhibition in second line,” said Gabe Sonke, MD, PhD, during his presentation at the meeting.

CDK4/6 inhibitors have shown benefit in both the first-and second-line setting, according to Dr. Sonke, who is a medical oncologist at the Netherlands Cancer Institute, Amsterdam. He added that most guidelines suggest use of CDK4/6 inhibitors in the first line, but there hasn’t been a direct comparison between use in the first and second line.

“Many patients do very well on endocrine therapy alone [in the first line]. Combination treatment leads to a higher risk of the emergence of resistant patterns such as ESR1 mutations, and CDK4/6 inhibitors also come with added costs and toxicities. Given the absence of comparative data between first line and second line, we designed the SONIA trial,” said Dr. Sonke.
 

Study methods and results

The researchers recruited 1,050 pre- and postmenopausal women who were randomized to a nonsteroidal AI in the first line followed by second-line CDK4/6i plus the estrogen receptor antagonist fulvestrant, or a nonsteroidal AI plus a CDK4/6i in the first line and fulvestrant in the second line. The most commonly used CDK4/6i was palbociclib at 91%, followed by ribociclib at 8%, and abemaciclib at 1%.

After a median follow-up of 37.3 months, the median duration of CDK4/6i exposure was 24.6 months in the first-line CDK4/6i group and 8.1 months in the second-line CDK4/6i group.

The median PFS during first-line therapy was 24.7 months in the first-line CDK4/6i group and 16.1 months in the second-line CDK4/6i group (hazard ratio, 0.59; P < .0001), which was consistent with the results seen in CDK4/6i pivotal trials in the first-line setting, according to Dr. Sonke. However, PFS after two lines of therapy was not significantly different between the groups (31.0 months vs. 26.8 months, respectively; HR, 0.87; P =.10).

The safety profile was similar to what had been seen in previous trials with respect to adverse events like bone marrow and liver function abnormalities and fatigue, but there were 42% more grade 3 or higher adverse events in the first-line CDK4/6i group than in the second-line CDK4/6i group. Dr. Sonke estimated that the increase in costs related to adverse events amounted to about $200,000 per patient receiving CDK4/6i as first line.

There were no significant differences between the two groups in quality of life measurement.

Subgroup analyses of patient categories including prior adjuvant or neoadjuvant chemotherapy or endocrine therapy, de novo metastatic disease, visceral disease, bone-only disease, and treatment with palbociclib or ribociclib showed no difference in outcome for first- versus second-line CDK4/6i treatment.
 

Are CDK4/6i costs and side effects worth it?

The findings challenge the need for using CDK4/6 inhibitors as first-line treatment in this population, according to Dr. Sonke, who also raised the following related questions.

“If you were a patient, would you consider a treatment that offers no improvement in quality of life and does not improve overall survival? As a doctor or nurse, would you recommend such a treatment to your patient that nearly doubles the incidence of side effects? And if you were responsible for covering the costs of this treatment, whether as an individual or health care insurance, would you consider it worth $200,000?”

For many patients, particularly in the first line setting where resistance mechanisms are less prevalent, endocrine therapy alone remains an excellent option,” said Dr. Sonke during his presentation.

During the discussion portion of the session, Daniel Stover, MD, who is an associate professor of translational therapeutics at Ohio State University Comprehensive Cancer Center, Columbus, pointed out that the lack of differences in the subanalyses leaves little guidance for physicians.

“We really have a limited signal on who can delay CDK4/6 inhibitors. I think one of the most important outcomes of this study is the focus on the patient, as there were substantially fewer adverse events and of course we need to think about financial toxicity as well,” he said. “I think one of the things that is perhaps most exciting to think about is who are the very good risk patients who can delay CDK4/6 inhibitor [therapy]? I think for the majority of patients, endocrine therapy plus CDK4/6 inhibitor is still the appropriate treatment, but I would argue we need additional biomarkers, be it RNA-based biomarkers, novel PET imaging, or perhaps [circulating tumor] DNA dynamics.”
 

Do cost savings and reduced side effects outweigh first-line PFS benefit?

During the question-and-answer session, William Sikov, MD, spoke up from the audience in support of Dr. Sonke’s conclusions.

“Clearly there are still patients who benefit from that approach, but I think that we have reached an inflection point: I posit that the question has now changed. [We should not ask] why a certain patient should not receive a CDK4/6 inhibitor, but why a certain patient should receive a CDK4/6 inhibitor in the first-line setting,” said Dr. Sikov, who is professor of medicine at Brown University, Providence, R.I.

Dr. Sonke agreed that first-line CDK4/6i is appropriate for some patients, and later echoed the need for biomarkers, but he said that researchers have so far had little luck in identifying any.

“Of course, it’s a shared decision-making between the patient and a doctor, but I think the baseline would be for all of us to consider first line single-agent endocrine therapy,” he said.

Session comoderator Michael Danso, MD, praised the trial but questioned whether the strategy would be adopted in places like the United States, where cost savings is not a major emphasis.

“Progression-free survival is so significant in the first line setting that I can’t imagine that many oncologists in the U.S. will adopt this approach. The other thing is that this was [almost] all palbociclib, so the question remains, would having a different cyclin dependent kinase inhibitor result in the same results? I think the jury’s still out,” said Dr. Danso, who is the research director at Virginia Oncology Associates, Norfolk.

The study was funded by the Dutch government and Dutch Health Insurers. Dr. Sonke has consulted for or advised Biovica, Novartis, and Seagen. He has received research support through his institution from Agendia, AstraZeneca/Merck, Merck Sharp & Dohme, Novartis, Roche, and Seagen. Dr. Sikov has been a speaker for Lilly. Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen.

CHICAGO – Patients with advanced estrogen receptor–positive, HER-negative breast cancer receiving first line treatment with CDK4/6 inhibitors (CDK4/6i) experienced no progression-free survival (PFS) or overall survival (OS) advantages over those who received the same therapy as second line treatment.

That was the conclusion of the phase 3 SONIA study, which was presented at the annual meeting of the American Society of Clinical Oncology.

The benefit from first line therapy is not maintained and almost completely disappears when patients in the control arm cross over to receive CDK4/6 inhibition in second line,” said Gabe Sonke, MD, PhD, during his presentation at the meeting.

CDK4/6 inhibitors have shown benefit in both the first-and second-line setting, according to Dr. Sonke, who is a medical oncologist at the Netherlands Cancer Institute, Amsterdam. He added that most guidelines suggest use of CDK4/6 inhibitors in the first line, but there hasn’t been a direct comparison between use in the first and second line.

“Many patients do very well on endocrine therapy alone [in the first line]. Combination treatment leads to a higher risk of the emergence of resistant patterns such as ESR1 mutations, and CDK4/6 inhibitors also come with added costs and toxicities. Given the absence of comparative data between first line and second line, we designed the SONIA trial,” said Dr. Sonke.
 

Study methods and results

The researchers recruited 1,050 pre- and postmenopausal women who were randomized to a nonsteroidal AI in the first line followed by second-line CDK4/6i plus the estrogen receptor antagonist fulvestrant, or a nonsteroidal AI plus a CDK4/6i in the first line and fulvestrant in the second line. The most commonly used CDK4/6i was palbociclib at 91%, followed by ribociclib at 8%, and abemaciclib at 1%.

After a median follow-up of 37.3 months, the median duration of CDK4/6i exposure was 24.6 months in the first-line CDK4/6i group and 8.1 months in the second-line CDK4/6i group.

The median PFS during first-line therapy was 24.7 months in the first-line CDK4/6i group and 16.1 months in the second-line CDK4/6i group (hazard ratio, 0.59; P < .0001), which was consistent with the results seen in CDK4/6i pivotal trials in the first-line setting, according to Dr. Sonke. However, PFS after two lines of therapy was not significantly different between the groups (31.0 months vs. 26.8 months, respectively; HR, 0.87; P =.10).

The safety profile was similar to what had been seen in previous trials with respect to adverse events like bone marrow and liver function abnormalities and fatigue, but there were 42% more grade 3 or higher adverse events in the first-line CDK4/6i group than in the second-line CDK4/6i group. Dr. Sonke estimated that the increase in costs related to adverse events amounted to about $200,000 per patient receiving CDK4/6i as first line.

There were no significant differences between the two groups in quality of life measurement.

Subgroup analyses of patient categories including prior adjuvant or neoadjuvant chemotherapy or endocrine therapy, de novo metastatic disease, visceral disease, bone-only disease, and treatment with palbociclib or ribociclib showed no difference in outcome for first- versus second-line CDK4/6i treatment.
 

Are CDK4/6i costs and side effects worth it?

The findings challenge the need for using CDK4/6 inhibitors as first-line treatment in this population, according to Dr. Sonke, who also raised the following related questions.

“If you were a patient, would you consider a treatment that offers no improvement in quality of life and does not improve overall survival? As a doctor or nurse, would you recommend such a treatment to your patient that nearly doubles the incidence of side effects? And if you were responsible for covering the costs of this treatment, whether as an individual or health care insurance, would you consider it worth $200,000?”

For many patients, particularly in the first line setting where resistance mechanisms are less prevalent, endocrine therapy alone remains an excellent option,” said Dr. Sonke during his presentation.

During the discussion portion of the session, Daniel Stover, MD, who is an associate professor of translational therapeutics at Ohio State University Comprehensive Cancer Center, Columbus, pointed out that the lack of differences in the subanalyses leaves little guidance for physicians.

“We really have a limited signal on who can delay CDK4/6 inhibitors. I think one of the most important outcomes of this study is the focus on the patient, as there were substantially fewer adverse events and of course we need to think about financial toxicity as well,” he said. “I think one of the things that is perhaps most exciting to think about is who are the very good risk patients who can delay CDK4/6 inhibitor [therapy]? I think for the majority of patients, endocrine therapy plus CDK4/6 inhibitor is still the appropriate treatment, but I would argue we need additional biomarkers, be it RNA-based biomarkers, novel PET imaging, or perhaps [circulating tumor] DNA dynamics.”
 

Do cost savings and reduced side effects outweigh first-line PFS benefit?

During the question-and-answer session, William Sikov, MD, spoke up from the audience in support of Dr. Sonke’s conclusions.

“Clearly there are still patients who benefit from that approach, but I think that we have reached an inflection point: I posit that the question has now changed. [We should not ask] why a certain patient should not receive a CDK4/6 inhibitor, but why a certain patient should receive a CDK4/6 inhibitor in the first-line setting,” said Dr. Sikov, who is professor of medicine at Brown University, Providence, R.I.

Dr. Sonke agreed that first-line CDK4/6i is appropriate for some patients, and later echoed the need for biomarkers, but he said that researchers have so far had little luck in identifying any.

“Of course, it’s a shared decision-making between the patient and a doctor, but I think the baseline would be for all of us to consider first line single-agent endocrine therapy,” he said.

Session comoderator Michael Danso, MD, praised the trial but questioned whether the strategy would be adopted in places like the United States, where cost savings is not a major emphasis.

“Progression-free survival is so significant in the first line setting that I can’t imagine that many oncologists in the U.S. will adopt this approach. The other thing is that this was [almost] all palbociclib, so the question remains, would having a different cyclin dependent kinase inhibitor result in the same results? I think the jury’s still out,” said Dr. Danso, who is the research director at Virginia Oncology Associates, Norfolk.

The study was funded by the Dutch government and Dutch Health Insurers. Dr. Sonke has consulted for or advised Biovica, Novartis, and Seagen. He has received research support through his institution from Agendia, AstraZeneca/Merck, Merck Sharp & Dohme, Novartis, Roche, and Seagen. Dr. Sikov has been a speaker for Lilly. Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen.

CHICAGO – Patients with advanced estrogen receptor–positive, HER-negative breast cancer receiving first line treatment with CDK4/6 inhibitors (CDK4/6i) experienced no progression-free survival (PFS) or overall survival (OS) advantages over those who received the same therapy as second line treatment.

That was the conclusion of the phase 3 SONIA study, which was presented at the annual meeting of the American Society of Clinical Oncology.

The benefit from first line therapy is not maintained and almost completely disappears when patients in the control arm cross over to receive CDK4/6 inhibition in second line,” said Gabe Sonke, MD, PhD, during his presentation at the meeting.

CDK4/6 inhibitors have shown benefit in both the first-and second-line setting, according to Dr. Sonke, who is a medical oncologist at the Netherlands Cancer Institute, Amsterdam. He added that most guidelines suggest use of CDK4/6 inhibitors in the first line, but there hasn’t been a direct comparison between use in the first and second line.

“Many patients do very well on endocrine therapy alone [in the first line]. Combination treatment leads to a higher risk of the emergence of resistant patterns such as ESR1 mutations, and CDK4/6 inhibitors also come with added costs and toxicities. Given the absence of comparative data between first line and second line, we designed the SONIA trial,” said Dr. Sonke.
 

Study methods and results

The researchers recruited 1,050 pre- and postmenopausal women who were randomized to a nonsteroidal AI in the first line followed by second-line CDK4/6i plus the estrogen receptor antagonist fulvestrant, or a nonsteroidal AI plus a CDK4/6i in the first line and fulvestrant in the second line. The most commonly used CDK4/6i was palbociclib at 91%, followed by ribociclib at 8%, and abemaciclib at 1%.

After a median follow-up of 37.3 months, the median duration of CDK4/6i exposure was 24.6 months in the first-line CDK4/6i group and 8.1 months in the second-line CDK4/6i group.

The median PFS during first-line therapy was 24.7 months in the first-line CDK4/6i group and 16.1 months in the second-line CDK4/6i group (hazard ratio, 0.59; P < .0001), which was consistent with the results seen in CDK4/6i pivotal trials in the first-line setting, according to Dr. Sonke. However, PFS after two lines of therapy was not significantly different between the groups (31.0 months vs. 26.8 months, respectively; HR, 0.87; P =.10).

The safety profile was similar to what had been seen in previous trials with respect to adverse events like bone marrow and liver function abnormalities and fatigue, but there were 42% more grade 3 or higher adverse events in the first-line CDK4/6i group than in the second-line CDK4/6i group. Dr. Sonke estimated that the increase in costs related to adverse events amounted to about $200,000 per patient receiving CDK4/6i as first line.

There were no significant differences between the two groups in quality of life measurement.

Subgroup analyses of patient categories including prior adjuvant or neoadjuvant chemotherapy or endocrine therapy, de novo metastatic disease, visceral disease, bone-only disease, and treatment with palbociclib or ribociclib showed no difference in outcome for first- versus second-line CDK4/6i treatment.
 

Are CDK4/6i costs and side effects worth it?

The findings challenge the need for using CDK4/6 inhibitors as first-line treatment in this population, according to Dr. Sonke, who also raised the following related questions.

“If you were a patient, would you consider a treatment that offers no improvement in quality of life and does not improve overall survival? As a doctor or nurse, would you recommend such a treatment to your patient that nearly doubles the incidence of side effects? And if you were responsible for covering the costs of this treatment, whether as an individual or health care insurance, would you consider it worth $200,000?”

For many patients, particularly in the first line setting where resistance mechanisms are less prevalent, endocrine therapy alone remains an excellent option,” said Dr. Sonke during his presentation.

During the discussion portion of the session, Daniel Stover, MD, who is an associate professor of translational therapeutics at Ohio State University Comprehensive Cancer Center, Columbus, pointed out that the lack of differences in the subanalyses leaves little guidance for physicians.

“We really have a limited signal on who can delay CDK4/6 inhibitors. I think one of the most important outcomes of this study is the focus on the patient, as there were substantially fewer adverse events and of course we need to think about financial toxicity as well,” he said. “I think one of the things that is perhaps most exciting to think about is who are the very good risk patients who can delay CDK4/6 inhibitor [therapy]? I think for the majority of patients, endocrine therapy plus CDK4/6 inhibitor is still the appropriate treatment, but I would argue we need additional biomarkers, be it RNA-based biomarkers, novel PET imaging, or perhaps [circulating tumor] DNA dynamics.”
 

Do cost savings and reduced side effects outweigh first-line PFS benefit?

During the question-and-answer session, William Sikov, MD, spoke up from the audience in support of Dr. Sonke’s conclusions.

“Clearly there are still patients who benefit from that approach, but I think that we have reached an inflection point: I posit that the question has now changed. [We should not ask] why a certain patient should not receive a CDK4/6 inhibitor, but why a certain patient should receive a CDK4/6 inhibitor in the first-line setting,” said Dr. Sikov, who is professor of medicine at Brown University, Providence, R.I.

Dr. Sonke agreed that first-line CDK4/6i is appropriate for some patients, and later echoed the need for biomarkers, but he said that researchers have so far had little luck in identifying any.

“Of course, it’s a shared decision-making between the patient and a doctor, but I think the baseline would be for all of us to consider first line single-agent endocrine therapy,” he said.

Session comoderator Michael Danso, MD, praised the trial but questioned whether the strategy would be adopted in places like the United States, where cost savings is not a major emphasis.

“Progression-free survival is so significant in the first line setting that I can’t imagine that many oncologists in the U.S. will adopt this approach. The other thing is that this was [almost] all palbociclib, so the question remains, would having a different cyclin dependent kinase inhibitor result in the same results? I think the jury’s still out,” said Dr. Danso, who is the research director at Virginia Oncology Associates, Norfolk.

The study was funded by the Dutch government and Dutch Health Insurers. Dr. Sonke has consulted for or advised Biovica, Novartis, and Seagen. He has received research support through his institution from Agendia, AstraZeneca/Merck, Merck Sharp & Dohme, Novartis, Roche, and Seagen. Dr. Sikov has been a speaker for Lilly. Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen.

The combination of ribociclib (Kisqali) and endocrine therapy has already been shown to yield a significant survival advantage for women with metastatic, hormone receptor–positive, HER2-negative (HR+/HER2–) breast cancer. Now the same combination has also shown benefit in early-stage HR+/HER2– breast tumors.

The new results come from an interim analysis of the phase 3, randomized NATALEE trial, which is comparing maintenance therapy with the (CDK4/6 inhibitor ribociclib plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone.

At a median follow-up of 27.7 months, the 3-year invasive disease–free survival (IDFS) rate was 90.4% for patients who received the combination, compared with 87.1% for patients who received endocrine therapy alone.

This difference translates into a 25% relative reduction in risk for recurrence with the addition of ribociclib, said principal investigator Dennis J. Slamon, MD, PhD, from the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

“The NATALEE results, in summary, do support this as a new treatment of choice available to physicians and patients for this broad population of patients with stage II or stage III hormone receptor–positive, HER2-negative disease in early breast cancer,” he said.

Dr. Slamon was speaking at a media briefing held prior to the annual meeting of the American Society of Clinical Oncology, where the results were presented
 

‘Early but impressive’

“Today, Dr. Slamon has shown us early but impressive data demonstrating a significant reduction in the risk of recurrence as defined by an improvement of invasive disease–free survival for patients with high-risk, node-positive and node-negative hormone receptor–positive, HER2-negative early breast cancer,” commented ASCO expert Rita Nanda, MD, director of the breast oncology program at the University of Chicago.

“We know that a substantial proportion of patients with early-stage hormone receptor–positive breast [cancer] can go on to recur,” Dr. Nanda continued. “These recurrences can be quite delayed, and for our patients with node-negative disease, to this point, we haven’t seen any improvements with the addition of a CDK4/6 inhibitor to endocrine therapy for early-stage breast cancer. Dr Slamon has also shown us that ribociclib in the context of the NATALEE trial is effective, it was well tolerated, and I do expect that these trial results will change practice.”

In a comment, Sylvia Adams, MD, a medical oncologist who specializes in breast cancer at the NYU Langone Perlmutter Cancer Center, New York, said she is comfortable with using a CDK4/6 inhibitor such as ribociclib or abemaciclib (Verzenio) in the adjuvant setting for patients with early, localized breast cancer.

She noted, however, that to date the absolute benefit of the combination over endocrine therapy alone has been modest, at 3.3%, but that the difference may be important to many patients who feel that they need to do everything they can to prevent disease recurrence.

“I’m really looking forward to the quality of life data, because it’s certainly known that any of these CDK4/6 inhibitors may add a bit of fatigue, and while there were no unexpected safety signals [in NATALEE], we know that there are some GI [gastrointestinal] effects with this therapy, as well as joint pain,” she said. “Joint pain is a little tricky, because the patients are also getting aromatase inhibitors, which can cause joint pain.”

In addition, premenopausal women in the study also received goserelin, an ovarian suppressor that triggers menopause, which is also associated with arthralgias, Dr. Adams said.

Dr. Adams and Dr. Nanda both noted that the addition of ribociclib to endocrine therapy increases the treatment burden for patients because it requires a commitment of at least 3 years and more frequent monitoring, especially in the first few months of therapy, compared with endocrine therapy alone.
 

Study details

The combination of ribociclib and standard of care endocrine therapy was the first to show an improvement in overall survival among women with metastatic HR+/HER2– breast cancer.

To see whether the combination could also benefit patients with early breast cancer, the investigators conducted NATALEE. They enrolled premenopausal and postmenopausal women and also men with HR+/HER2– breast cancer. Cases ranged from stage IIA (with either no nodal involvement with additional risk factors or with one to three involved axillary lymph nodes) to stage IIB-III disease, based on American Joint Committee on Cancer staging.

Patients who had previously received neoadjuvant or adjuvant endocrine therapy were accepted into the trial if the therapy had been started within 1 year of randomization.

The patients were stratified by age, menopausal status, disease stage, prior chemotherapy status, and geographic region. They were randomly assigned to receive either ribociclib 400 mg per day for 3 weeks, then were given 1 week off each cycle for 3 years plus endocrine therapy with either letrozole 2.5 mg/day or anastrozole 1 mg/day for at least 5 years, or to endocrine therapy alone. Men and premenopausal women also received goserelin.

Dr. Slamon noted that the 400-mg dose of ribociclib is lower than the recommended starting dose of 600 mg for metastatic disease. They chose the lower dose to allow longer duration of therapy, with a goal of achieving optimal disease suppression by driving tumor cells into irreversible senescence with less side effects.

A total of 2,549 patients were randomly assigned to receive the combination; 2,552 patients received endocrine therapy alone.

At the data cutoff on Jan. 11, 2023, after the prespecified minimum number of IDFS events had occurred, 189 patients in the ribociclib arm experienced recurrence, compared with 237 patients in the endocrine therapy–only arm.

As noted, 3-year IDFS rates were 90.4% with ribociclib and 87.1% with endocrine therapy alone, which translates to a hazard ratio of 0.748 in favor of the combination (P = .0014).

The benefit of ribociclib was generally consistent across subgroups, including node-negative patients, but there were too few patients in this subgroup for the differences to reach statistical significance, Dr. Slamon said.
 

Safety

The most commonly reported adverse event in the endocrine therapy–alone arm were joint pain and hot flashes

The most common adverse events with ribociclib included neutropenia and joint pain. Rates of gastrointestinal adverse events and fatigue, typical of CDK4/6 inhibitors, were relatively low in this study.

Dr. Slamon compared the rates of neutropenia with ribociclib in this trial to those in pooled data from the MONALEESA series of trials, in which ribociclib was delivered at a 600-mg dose. Grade 3 or 4 neutropenia occurred in 44% of patients in NATALEE, compared with 60% of patients in the MONALEESA trials.

In the ribociclib arm, 5.2% of patients experienced prolongation of the QT interval, compared with 1.2% of patients in the endocrine therapy–alone arm. No cases of torsades des pointes or problematic rhythm disturbances were observed, Dr. Slamon said.

“As frequently happens when we have these lovely, large, phase 3 registration trials but with some restriction in eligibility, when you get out to real-world practice, we don’t know what will happen in women who are on antiarrhythmics and if they’ll have a higher incidence of the QT elongation; they just weren’t included in the study. So it sounds like we’ll have to be paying attention to that,” commented briefing moderator Julie R. Gralow, MD, FACP, FASCO, chief medical officer and executive vice president of ASCO.

The study was funded by Novartis. Dr. Slamon has a leadership position with 1200 Pharma, Biomarin, and Torl Biotherapeutics, a consulting/advisory role for Novartis, and has received honoraria, research funding, and travel expenses from Novartis and others. Multiple coauthors reported financial relationships with Novartis and others. Dr. Nanda has had consulting/advisory roles with and has received institutional research funding from several companies, not including Novartis. Dr. Adams has participated on an advisory board for Cogent Biosciences and her institution has received research funding from various companies.

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

The combination of ribociclib (Kisqali) and endocrine therapy has already been shown to yield a significant survival advantage for women with metastatic, hormone receptor–positive, HER2-negative (HR+/HER2–) breast cancer. Now the same combination has also shown benefit in early-stage HR+/HER2– breast tumors.

The new results come from an interim analysis of the phase 3, randomized NATALEE trial, which is comparing maintenance therapy with the (CDK4/6 inhibitor ribociclib plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone.

At a median follow-up of 27.7 months, the 3-year invasive disease–free survival (IDFS) rate was 90.4% for patients who received the combination, compared with 87.1% for patients who received endocrine therapy alone.

This difference translates into a 25% relative reduction in risk for recurrence with the addition of ribociclib, said principal investigator Dennis J. Slamon, MD, PhD, from the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

“The NATALEE results, in summary, do support this as a new treatment of choice available to physicians and patients for this broad population of patients with stage II or stage III hormone receptor–positive, HER2-negative disease in early breast cancer,” he said.

Dr. Slamon was speaking at a media briefing held prior to the annual meeting of the American Society of Clinical Oncology, where the results were presented
 

‘Early but impressive’

“Today, Dr. Slamon has shown us early but impressive data demonstrating a significant reduction in the risk of recurrence as defined by an improvement of invasive disease–free survival for patients with high-risk, node-positive and node-negative hormone receptor–positive, HER2-negative early breast cancer,” commented ASCO expert Rita Nanda, MD, director of the breast oncology program at the University of Chicago.

“We know that a substantial proportion of patients with early-stage hormone receptor–positive breast [cancer] can go on to recur,” Dr. Nanda continued. “These recurrences can be quite delayed, and for our patients with node-negative disease, to this point, we haven’t seen any improvements with the addition of a CDK4/6 inhibitor to endocrine therapy for early-stage breast cancer. Dr Slamon has also shown us that ribociclib in the context of the NATALEE trial is effective, it was well tolerated, and I do expect that these trial results will change practice.”

In a comment, Sylvia Adams, MD, a medical oncologist who specializes in breast cancer at the NYU Langone Perlmutter Cancer Center, New York, said she is comfortable with using a CDK4/6 inhibitor such as ribociclib or abemaciclib (Verzenio) in the adjuvant setting for patients with early, localized breast cancer.

She noted, however, that to date the absolute benefit of the combination over endocrine therapy alone has been modest, at 3.3%, but that the difference may be important to many patients who feel that they need to do everything they can to prevent disease recurrence.

“I’m really looking forward to the quality of life data, because it’s certainly known that any of these CDK4/6 inhibitors may add a bit of fatigue, and while there were no unexpected safety signals [in NATALEE], we know that there are some GI [gastrointestinal] effects with this therapy, as well as joint pain,” she said. “Joint pain is a little tricky, because the patients are also getting aromatase inhibitors, which can cause joint pain.”

In addition, premenopausal women in the study also received goserelin, an ovarian suppressor that triggers menopause, which is also associated with arthralgias, Dr. Adams said.

Dr. Adams and Dr. Nanda both noted that the addition of ribociclib to endocrine therapy increases the treatment burden for patients because it requires a commitment of at least 3 years and more frequent monitoring, especially in the first few months of therapy, compared with endocrine therapy alone.
 

Study details

The combination of ribociclib and standard of care endocrine therapy was the first to show an improvement in overall survival among women with metastatic HR+/HER2– breast cancer.

To see whether the combination could also benefit patients with early breast cancer, the investigators conducted NATALEE. They enrolled premenopausal and postmenopausal women and also men with HR+/HER2– breast cancer. Cases ranged from stage IIA (with either no nodal involvement with additional risk factors or with one to three involved axillary lymph nodes) to stage IIB-III disease, based on American Joint Committee on Cancer staging.

Patients who had previously received neoadjuvant or adjuvant endocrine therapy were accepted into the trial if the therapy had been started within 1 year of randomization.

The patients were stratified by age, menopausal status, disease stage, prior chemotherapy status, and geographic region. They were randomly assigned to receive either ribociclib 400 mg per day for 3 weeks, then were given 1 week off each cycle for 3 years plus endocrine therapy with either letrozole 2.5 mg/day or anastrozole 1 mg/day for at least 5 years, or to endocrine therapy alone. Men and premenopausal women also received goserelin.

Dr. Slamon noted that the 400-mg dose of ribociclib is lower than the recommended starting dose of 600 mg for metastatic disease. They chose the lower dose to allow longer duration of therapy, with a goal of achieving optimal disease suppression by driving tumor cells into irreversible senescence with less side effects.

A total of 2,549 patients were randomly assigned to receive the combination; 2,552 patients received endocrine therapy alone.

At the data cutoff on Jan. 11, 2023, after the prespecified minimum number of IDFS events had occurred, 189 patients in the ribociclib arm experienced recurrence, compared with 237 patients in the endocrine therapy–only arm.

As noted, 3-year IDFS rates were 90.4% with ribociclib and 87.1% with endocrine therapy alone, which translates to a hazard ratio of 0.748 in favor of the combination (P = .0014).

The benefit of ribociclib was generally consistent across subgroups, including node-negative patients, but there were too few patients in this subgroup for the differences to reach statistical significance, Dr. Slamon said.
 

Safety

The most commonly reported adverse event in the endocrine therapy–alone arm were joint pain and hot flashes

The most common adverse events with ribociclib included neutropenia and joint pain. Rates of gastrointestinal adverse events and fatigue, typical of CDK4/6 inhibitors, were relatively low in this study.

Dr. Slamon compared the rates of neutropenia with ribociclib in this trial to those in pooled data from the MONALEESA series of trials, in which ribociclib was delivered at a 600-mg dose. Grade 3 or 4 neutropenia occurred in 44% of patients in NATALEE, compared with 60% of patients in the MONALEESA trials.

In the ribociclib arm, 5.2% of patients experienced prolongation of the QT interval, compared with 1.2% of patients in the endocrine therapy–alone arm. No cases of torsades des pointes or problematic rhythm disturbances were observed, Dr. Slamon said.

“As frequently happens when we have these lovely, large, phase 3 registration trials but with some restriction in eligibility, when you get out to real-world practice, we don’t know what will happen in women who are on antiarrhythmics and if they’ll have a higher incidence of the QT elongation; they just weren’t included in the study. So it sounds like we’ll have to be paying attention to that,” commented briefing moderator Julie R. Gralow, MD, FACP, FASCO, chief medical officer and executive vice president of ASCO.

The study was funded by Novartis. Dr. Slamon has a leadership position with 1200 Pharma, Biomarin, and Torl Biotherapeutics, a consulting/advisory role for Novartis, and has received honoraria, research funding, and travel expenses from Novartis and others. Multiple coauthors reported financial relationships with Novartis and others. Dr. Nanda has had consulting/advisory roles with and has received institutional research funding from several companies, not including Novartis. Dr. Adams has participated on an advisory board for Cogent Biosciences and her institution has received research funding from various companies.

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

The combination of ribociclib (Kisqali) and endocrine therapy has already been shown to yield a significant survival advantage for women with metastatic, hormone receptor–positive, HER2-negative (HR+/HER2–) breast cancer. Now the same combination has also shown benefit in early-stage HR+/HER2– breast tumors.

The new results come from an interim analysis of the phase 3, randomized NATALEE trial, which is comparing maintenance therapy with the (CDK4/6 inhibitor ribociclib plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone.

At a median follow-up of 27.7 months, the 3-year invasive disease–free survival (IDFS) rate was 90.4% for patients who received the combination, compared with 87.1% for patients who received endocrine therapy alone.

This difference translates into a 25% relative reduction in risk for recurrence with the addition of ribociclib, said principal investigator Dennis J. Slamon, MD, PhD, from the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.

“The NATALEE results, in summary, do support this as a new treatment of choice available to physicians and patients for this broad population of patients with stage II or stage III hormone receptor–positive, HER2-negative disease in early breast cancer,” he said.

Dr. Slamon was speaking at a media briefing held prior to the annual meeting of the American Society of Clinical Oncology, where the results were presented
 

‘Early but impressive’

“Today, Dr. Slamon has shown us early but impressive data demonstrating a significant reduction in the risk of recurrence as defined by an improvement of invasive disease–free survival for patients with high-risk, node-positive and node-negative hormone receptor–positive, HER2-negative early breast cancer,” commented ASCO expert Rita Nanda, MD, director of the breast oncology program at the University of Chicago.

“We know that a substantial proportion of patients with early-stage hormone receptor–positive breast [cancer] can go on to recur,” Dr. Nanda continued. “These recurrences can be quite delayed, and for our patients with node-negative disease, to this point, we haven’t seen any improvements with the addition of a CDK4/6 inhibitor to endocrine therapy for early-stage breast cancer. Dr Slamon has also shown us that ribociclib in the context of the NATALEE trial is effective, it was well tolerated, and I do expect that these trial results will change practice.”

In a comment, Sylvia Adams, MD, a medical oncologist who specializes in breast cancer at the NYU Langone Perlmutter Cancer Center, New York, said she is comfortable with using a CDK4/6 inhibitor such as ribociclib or abemaciclib (Verzenio) in the adjuvant setting for patients with early, localized breast cancer.

She noted, however, that to date the absolute benefit of the combination over endocrine therapy alone has been modest, at 3.3%, but that the difference may be important to many patients who feel that they need to do everything they can to prevent disease recurrence.

“I’m really looking forward to the quality of life data, because it’s certainly known that any of these CDK4/6 inhibitors may add a bit of fatigue, and while there were no unexpected safety signals [in NATALEE], we know that there are some GI [gastrointestinal] effects with this therapy, as well as joint pain,” she said. “Joint pain is a little tricky, because the patients are also getting aromatase inhibitors, which can cause joint pain.”

In addition, premenopausal women in the study also received goserelin, an ovarian suppressor that triggers menopause, which is also associated with arthralgias, Dr. Adams said.

Dr. Adams and Dr. Nanda both noted that the addition of ribociclib to endocrine therapy increases the treatment burden for patients because it requires a commitment of at least 3 years and more frequent monitoring, especially in the first few months of therapy, compared with endocrine therapy alone.
 

Study details

The combination of ribociclib and standard of care endocrine therapy was the first to show an improvement in overall survival among women with metastatic HR+/HER2– breast cancer.

To see whether the combination could also benefit patients with early breast cancer, the investigators conducted NATALEE. They enrolled premenopausal and postmenopausal women and also men with HR+/HER2– breast cancer. Cases ranged from stage IIA (with either no nodal involvement with additional risk factors or with one to three involved axillary lymph nodes) to stage IIB-III disease, based on American Joint Committee on Cancer staging.

Patients who had previously received neoadjuvant or adjuvant endocrine therapy were accepted into the trial if the therapy had been started within 1 year of randomization.

The patients were stratified by age, menopausal status, disease stage, prior chemotherapy status, and geographic region. They were randomly assigned to receive either ribociclib 400 mg per day for 3 weeks, then were given 1 week off each cycle for 3 years plus endocrine therapy with either letrozole 2.5 mg/day or anastrozole 1 mg/day for at least 5 years, or to endocrine therapy alone. Men and premenopausal women also received goserelin.

Dr. Slamon noted that the 400-mg dose of ribociclib is lower than the recommended starting dose of 600 mg for metastatic disease. They chose the lower dose to allow longer duration of therapy, with a goal of achieving optimal disease suppression by driving tumor cells into irreversible senescence with less side effects.

A total of 2,549 patients were randomly assigned to receive the combination; 2,552 patients received endocrine therapy alone.

At the data cutoff on Jan. 11, 2023, after the prespecified minimum number of IDFS events had occurred, 189 patients in the ribociclib arm experienced recurrence, compared with 237 patients in the endocrine therapy–only arm.

As noted, 3-year IDFS rates were 90.4% with ribociclib and 87.1% with endocrine therapy alone, which translates to a hazard ratio of 0.748 in favor of the combination (P = .0014).

The benefit of ribociclib was generally consistent across subgroups, including node-negative patients, but there were too few patients in this subgroup for the differences to reach statistical significance, Dr. Slamon said.
 

Safety

The most commonly reported adverse event in the endocrine therapy–alone arm were joint pain and hot flashes

The most common adverse events with ribociclib included neutropenia and joint pain. Rates of gastrointestinal adverse events and fatigue, typical of CDK4/6 inhibitors, were relatively low in this study.

Dr. Slamon compared the rates of neutropenia with ribociclib in this trial to those in pooled data from the MONALEESA series of trials, in which ribociclib was delivered at a 600-mg dose. Grade 3 or 4 neutropenia occurred in 44% of patients in NATALEE, compared with 60% of patients in the MONALEESA trials.

In the ribociclib arm, 5.2% of patients experienced prolongation of the QT interval, compared with 1.2% of patients in the endocrine therapy–alone arm. No cases of torsades des pointes or problematic rhythm disturbances were observed, Dr. Slamon said.

“As frequently happens when we have these lovely, large, phase 3 registration trials but with some restriction in eligibility, when you get out to real-world practice, we don’t know what will happen in women who are on antiarrhythmics and if they’ll have a higher incidence of the QT elongation; they just weren’t included in the study. So it sounds like we’ll have to be paying attention to that,” commented briefing moderator Julie R. Gralow, MD, FACP, FASCO, chief medical officer and executive vice president of ASCO.

The study was funded by Novartis. Dr. Slamon has a leadership position with 1200 Pharma, Biomarin, and Torl Biotherapeutics, a consulting/advisory role for Novartis, and has received honoraria, research funding, and travel expenses from Novartis and others. Multiple coauthors reported financial relationships with Novartis and others. Dr. Nanda has had consulting/advisory roles with and has received institutional research funding from several companies, not including Novartis. Dr. Adams has participated on an advisory board for Cogent Biosciences and her institution has received research funding from various companies.

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

A telephone-based weight loss intervention resulted in clinically meaningful weight loss in patients with breast cancer who were overweight and obese.

The finding comes from a case-control study of 3,136 women who had been diagnosed with stage II or III breast cancer. The average body mass index of participants was 34.5 kg/m², and mean age was 53.4 years.

After 6 months, patients who received telephone coaching as well as health education lost 4.4 kg (9.7 lb), which was 4.8% of their baseline body weight.

In contrast, patients in the control group, who received only health education, gained 0.2 kg (0.3% of their baseline body weight) over the same period.

At the 1-year mark, the telephone weight loss intervention group had maintained the weight they lost at 6 months, whereas the control group gained even more weight and ended with a 0.9% weight gain.

“This equated to a 5.56% weight differential in the two arms demonstrating significant weight loss, which was also clinically significant given that a 3% weight loss is sufficient to improve diabetes and other chronic diseases,” commented lead author Jennifer Ligibel, MD, associate professor of medicine at the Dana-Farber Cancer Institute in Boston. 

She spoke at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study was presented.

“Our study provides compelling evidence that weight loss interventions can successfully reduce weight in a diverse population of patients with breast cancer,” she said in a statement. At the time of diagnosis, 57% of patients were postmenopausal, 80.3% were White, 12.8% were Black, and 7.3% were Hispanic. 

Patients in the intervention group received a health education program plus a 2-year telephone-based weight loss program that focused on lowering calorie intake and increasing physical activity.

Those in the control group only received the health education program that included nontailored diet and exercise materials, a quarterly newsletter, twice-yearly webinars, and a subscription to a health magazine of the participant’s choosing

“This study was delivered completely remotely and it was done so purposefully because we wanted to develop a program that could work for somebody who lived in a rural area in the middle of the country, as well as it could for somebody who lived close to a cancer center,” Dr. Ligibel commented.

“The next step will be to determine whether this weight loss translates into lower rates of cancer recurrence and mortality. If our trial is successful in improving cancer outcomes, it will have far-reaching implications, demonstrating that weight loss should be incorporated into the standard of care for survivors of breast cancer,” she added.

Commenting on the new findings, ASCO expert Elizabeth Anne Comen, MD, Memorial Sloan Kettering Cancer Center, New York, said: “This study demonstrates that consistent health coaching by telephone – a more accessible, cost-effective approach compared to in-person programs – can significantly help patients with breast cancer lose weight over 1 year and is effective across diverse groups of patients.

“We anxiously await longer-term follow-up to see whether this weight reduction will ultimately improve outcomes for these patients,” she added.

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

A telephone-based weight loss intervention resulted in clinically meaningful weight loss in patients with breast cancer who were overweight and obese.

The finding comes from a case-control study of 3,136 women who had been diagnosed with stage II or III breast cancer. The average body mass index of participants was 34.5 kg/m², and mean age was 53.4 years.

After 6 months, patients who received telephone coaching as well as health education lost 4.4 kg (9.7 lb), which was 4.8% of their baseline body weight.

In contrast, patients in the control group, who received only health education, gained 0.2 kg (0.3% of their baseline body weight) over the same period.

At the 1-year mark, the telephone weight loss intervention group had maintained the weight they lost at 6 months, whereas the control group gained even more weight and ended with a 0.9% weight gain.

“This equated to a 5.56% weight differential in the two arms demonstrating significant weight loss, which was also clinically significant given that a 3% weight loss is sufficient to improve diabetes and other chronic diseases,” commented lead author Jennifer Ligibel, MD, associate professor of medicine at the Dana-Farber Cancer Institute in Boston. 

She spoke at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study was presented.

“Our study provides compelling evidence that weight loss interventions can successfully reduce weight in a diverse population of patients with breast cancer,” she said in a statement. At the time of diagnosis, 57% of patients were postmenopausal, 80.3% were White, 12.8% were Black, and 7.3% were Hispanic. 

Patients in the intervention group received a health education program plus a 2-year telephone-based weight loss program that focused on lowering calorie intake and increasing physical activity.

Those in the control group only received the health education program that included nontailored diet and exercise materials, a quarterly newsletter, twice-yearly webinars, and a subscription to a health magazine of the participant’s choosing

“This study was delivered completely remotely and it was done so purposefully because we wanted to develop a program that could work for somebody who lived in a rural area in the middle of the country, as well as it could for somebody who lived close to a cancer center,” Dr. Ligibel commented.

“The next step will be to determine whether this weight loss translates into lower rates of cancer recurrence and mortality. If our trial is successful in improving cancer outcomes, it will have far-reaching implications, demonstrating that weight loss should be incorporated into the standard of care for survivors of breast cancer,” she added.

Commenting on the new findings, ASCO expert Elizabeth Anne Comen, MD, Memorial Sloan Kettering Cancer Center, New York, said: “This study demonstrates that consistent health coaching by telephone – a more accessible, cost-effective approach compared to in-person programs – can significantly help patients with breast cancer lose weight over 1 year and is effective across diverse groups of patients.

“We anxiously await longer-term follow-up to see whether this weight reduction will ultimately improve outcomes for these patients,” she added.

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

A telephone-based weight loss intervention resulted in clinically meaningful weight loss in patients with breast cancer who were overweight and obese.

The finding comes from a case-control study of 3,136 women who had been diagnosed with stage II or III breast cancer. The average body mass index of participants was 34.5 kg/m², and mean age was 53.4 years.

After 6 months, patients who received telephone coaching as well as health education lost 4.4 kg (9.7 lb), which was 4.8% of their baseline body weight.

In contrast, patients in the control group, who received only health education, gained 0.2 kg (0.3% of their baseline body weight) over the same period.

At the 1-year mark, the telephone weight loss intervention group had maintained the weight they lost at 6 months, whereas the control group gained even more weight and ended with a 0.9% weight gain.

“This equated to a 5.56% weight differential in the two arms demonstrating significant weight loss, which was also clinically significant given that a 3% weight loss is sufficient to improve diabetes and other chronic diseases,” commented lead author Jennifer Ligibel, MD, associate professor of medicine at the Dana-Farber Cancer Institute in Boston. 

She spoke at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study was presented.

“Our study provides compelling evidence that weight loss interventions can successfully reduce weight in a diverse population of patients with breast cancer,” she said in a statement. At the time of diagnosis, 57% of patients were postmenopausal, 80.3% were White, 12.8% were Black, and 7.3% were Hispanic. 

Patients in the intervention group received a health education program plus a 2-year telephone-based weight loss program that focused on lowering calorie intake and increasing physical activity.

Those in the control group only received the health education program that included nontailored diet and exercise materials, a quarterly newsletter, twice-yearly webinars, and a subscription to a health magazine of the participant’s choosing

“This study was delivered completely remotely and it was done so purposefully because we wanted to develop a program that could work for somebody who lived in a rural area in the middle of the country, as well as it could for somebody who lived close to a cancer center,” Dr. Ligibel commented.

“The next step will be to determine whether this weight loss translates into lower rates of cancer recurrence and mortality. If our trial is successful in improving cancer outcomes, it will have far-reaching implications, demonstrating that weight loss should be incorporated into the standard of care for survivors of breast cancer,” she added.

Commenting on the new findings, ASCO expert Elizabeth Anne Comen, MD, Memorial Sloan Kettering Cancer Center, New York, said: “This study demonstrates that consistent health coaching by telephone – a more accessible, cost-effective approach compared to in-person programs – can significantly help patients with breast cancer lose weight over 1 year and is effective across diverse groups of patients.

“We anxiously await longer-term follow-up to see whether this weight reduction will ultimately improve outcomes for these patients,” she added.

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

CHICAGO – Nearly all patients who were diverted from chemotherapy prior to surgery for HER2-positive early breast cancer survived without cancer recurrence for 3 years, according to new findings from a phase 2 trial.

The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).

“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.

As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.

The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
 

Study methods and results

At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).

At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.

The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.

Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.

In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”

Should clinicians embrace the study’s strategy, and what are the costs?

“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.

There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.

The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.

CHICAGO – Nearly all patients who were diverted from chemotherapy prior to surgery for HER2-positive early breast cancer survived without cancer recurrence for 3 years, according to new findings from a phase 2 trial.

The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).

“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.

As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.

The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
 

Study methods and results

At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).

At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.

The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.

Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.

In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”

Should clinicians embrace the study’s strategy, and what are the costs?

“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.

There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.

The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.

CHICAGO – Nearly all patients who were diverted from chemotherapy prior to surgery for HER2-positive early breast cancer survived without cancer recurrence for 3 years, according to new findings from a phase 2 trial.

The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).

“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.

As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.

The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
 

Study methods and results

At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).

At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.

The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.

Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.

In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”

Should clinicians embrace the study’s strategy, and what are the costs?

“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.

There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.

The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.

CHICAGO – A new meta-analysis of 25 studies dating back to 1948 provides more evidence linking ovarian suppression/ablation in premenopausal women to less recurrence and more survival in the long term after breast cancer.

Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.

The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.

The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.

Recently published research has supported hormone therapy targeting the ovaries in this population.

“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
 

Study methods and results

For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.

Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).

Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).

The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”

Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
 

Tamoxifen on its own seems to have powerful positive effect

The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.

The meta-analysis didn’t examine cost or cost-effectiveness.

Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.

Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.

“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”

According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”

It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.

No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.

CHICAGO – A new meta-analysis of 25 studies dating back to 1948 provides more evidence linking ovarian suppression/ablation in premenopausal women to less recurrence and more survival in the long term after breast cancer.

Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.

The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.

The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.

Recently published research has supported hormone therapy targeting the ovaries in this population.

“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
 

Study methods and results

For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.

Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).

Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).

The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”

Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
 

Tamoxifen on its own seems to have powerful positive effect

The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.

The meta-analysis didn’t examine cost or cost-effectiveness.

Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.

Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.

“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”

According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”

It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.

No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.

CHICAGO – A new meta-analysis of 25 studies dating back to 1948 provides more evidence linking ovarian suppression/ablation in premenopausal women to less recurrence and more survival in the long term after breast cancer.

Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.

The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.

The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.

Recently published research has supported hormone therapy targeting the ovaries in this population.

“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
 

Study methods and results

For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.

Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).

Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).

The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”

Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
 

Tamoxifen on its own seems to have powerful positive effect

The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.

The meta-analysis didn’t examine cost or cost-effectiveness.

Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.

Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.

“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”

According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”

It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.

No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.