Breast Cancer

CHICAGO – In a large case series of metastatic breast cancer patients with pseudocirrhosis, researchers found that almost all such patients had hormone receptor–positive (HR+) disease as well as extensive liver metastases. Pseudocirrhosis appears radiographically similar to cirrhosis, but lacks its classic pathologic features.

The study is the largest cohort of patients with pseudocirrhosis studied to date. “It provides important clinical information about the natural history of this condition to help oncologists better understand which patients develop this condition and what complications are most common. Interestingly, we found that patients who developed ascites had a worse overall survival than patients who did not develop ascites, which was not previously reported,” said Laura Huppert, MD, who presented the findings during a poster session at the annual meeting of the American Society of Clinical Oncology.

Pseudocirrhosis is commonly found in patients with metastatic breast cancer and can lead to ascites and varices, among other complications. “These problems can be quite debilitating and even life-threatening for our patients. In order to better diagnose and treat our patients with pseudocirrhosis, we first wanted to understand the natural history of this condition, including which patients develop it, what treatments they have received, and what complications are most frequent,” said Dr. Huppert, MD, who is a hematology/oncology fellow at the University of California, San Francisco.

The study was retrospective, making it impossible to determine causality. “It is possible that the biology of HR+ disease predisposes patients to the development of pseudocirrhosis through mechanisms that are not yet elucidated. Alternatively, this may be due to the fact that patients with HR+ disease tend to have longer survival and are on systemic therapy for longer periods of time, allowing more time for pseudocirrhosis to develop in response to systemic therapy,” Dr. Huppert said.

In future work, Dr. Huppert plans to examine a control arm of patients with liver disease who do not develop pseudocirrhosis to gain a better understanding of factors that might cause the condition. She also hopes to work with hepatologists to determine if new antifibrosis agents might be applicable to pseudocirrhosis. “There may be interesting things we can learn from other disease states and apply to this condition,” she said.

The researchers analyzed data from 120 patients with pseudocirrhosis. 82.5% of patients were HR+/HER2–, 11.7% were HR+/HER2+, 2.5% were HR–/HER2+, and 3.3% were triple negative. Liver metastases were present in all patients, and 82.5% had more than 15 liver lesions.

A total of 92.5% of patients had previously undergone chemotherapy before pseudocirrhosis was identified, and the median time to diagnosis of pseudocirrhosis after diagnosis of liver metastases was 18.7 months. 50% of patients with pseudocirrhosis had stable or responding disease. After pseudocirrhosis diagnosis, patients underwent a median of 1.0 additional lines of therapy, and the median overall survival following pseudocirrhosis diagnosis was 7.9 months. A total of 80.8% of patients went on to be diagnosed with ascites, 17.5% with esophageal varices, 21.7% with splenomegaly, 10.0% with gastrointestinal bleeding, and 9.2% with hepatic encephalopathy.

Patients with radiographic evidence of ascites survived an average of 42.8 months after metastatic breast cancer diagnosis, while those without ascites survived an average of 76.2 months (P < .001).

Specialty care was rare: Just 7.5% of patients received a GI/hepatology consultation.

Dr. Huppert has no relevant financial disclosures.

CHICAGO – In a large case series of metastatic breast cancer patients with pseudocirrhosis, researchers found that almost all such patients had hormone receptor–positive (HR+) disease as well as extensive liver metastases. Pseudocirrhosis appears radiographically similar to cirrhosis, but lacks its classic pathologic features.

The study is the largest cohort of patients with pseudocirrhosis studied to date. “It provides important clinical information about the natural history of this condition to help oncologists better understand which patients develop this condition and what complications are most common. Interestingly, we found that patients who developed ascites had a worse overall survival than patients who did not develop ascites, which was not previously reported,” said Laura Huppert, MD, who presented the findings during a poster session at the annual meeting of the American Society of Clinical Oncology.

Pseudocirrhosis is commonly found in patients with metastatic breast cancer and can lead to ascites and varices, among other complications. “These problems can be quite debilitating and even life-threatening for our patients. In order to better diagnose and treat our patients with pseudocirrhosis, we first wanted to understand the natural history of this condition, including which patients develop it, what treatments they have received, and what complications are most frequent,” said Dr. Huppert, MD, who is a hematology/oncology fellow at the University of California, San Francisco.

The study was retrospective, making it impossible to determine causality. “It is possible that the biology of HR+ disease predisposes patients to the development of pseudocirrhosis through mechanisms that are not yet elucidated. Alternatively, this may be due to the fact that patients with HR+ disease tend to have longer survival and are on systemic therapy for longer periods of time, allowing more time for pseudocirrhosis to develop in response to systemic therapy,” Dr. Huppert said.

In future work, Dr. Huppert plans to examine a control arm of patients with liver disease who do not develop pseudocirrhosis to gain a better understanding of factors that might cause the condition. She also hopes to work with hepatologists to determine if new antifibrosis agents might be applicable to pseudocirrhosis. “There may be interesting things we can learn from other disease states and apply to this condition,” she said.

The researchers analyzed data from 120 patients with pseudocirrhosis. 82.5% of patients were HR+/HER2–, 11.7% were HR+/HER2+, 2.5% were HR–/HER2+, and 3.3% were triple negative. Liver metastases were present in all patients, and 82.5% had more than 15 liver lesions.

A total of 92.5% of patients had previously undergone chemotherapy before pseudocirrhosis was identified, and the median time to diagnosis of pseudocirrhosis after diagnosis of liver metastases was 18.7 months. 50% of patients with pseudocirrhosis had stable or responding disease. After pseudocirrhosis diagnosis, patients underwent a median of 1.0 additional lines of therapy, and the median overall survival following pseudocirrhosis diagnosis was 7.9 months. A total of 80.8% of patients went on to be diagnosed with ascites, 17.5% with esophageal varices, 21.7% with splenomegaly, 10.0% with gastrointestinal bleeding, and 9.2% with hepatic encephalopathy.

Patients with radiographic evidence of ascites survived an average of 42.8 months after metastatic breast cancer diagnosis, while those without ascites survived an average of 76.2 months (P < .001).

Specialty care was rare: Just 7.5% of patients received a GI/hepatology consultation.

Dr. Huppert has no relevant financial disclosures.

CHICAGO – In a large case series of metastatic breast cancer patients with pseudocirrhosis, researchers found that almost all such patients had hormone receptor–positive (HR+) disease as well as extensive liver metastases. Pseudocirrhosis appears radiographically similar to cirrhosis, but lacks its classic pathologic features.

The study is the largest cohort of patients with pseudocirrhosis studied to date. “It provides important clinical information about the natural history of this condition to help oncologists better understand which patients develop this condition and what complications are most common. Interestingly, we found that patients who developed ascites had a worse overall survival than patients who did not develop ascites, which was not previously reported,” said Laura Huppert, MD, who presented the findings during a poster session at the annual meeting of the American Society of Clinical Oncology.

Pseudocirrhosis is commonly found in patients with metastatic breast cancer and can lead to ascites and varices, among other complications. “These problems can be quite debilitating and even life-threatening for our patients. In order to better diagnose and treat our patients with pseudocirrhosis, we first wanted to understand the natural history of this condition, including which patients develop it, what treatments they have received, and what complications are most frequent,” said Dr. Huppert, MD, who is a hematology/oncology fellow at the University of California, San Francisco.

The study was retrospective, making it impossible to determine causality. “It is possible that the biology of HR+ disease predisposes patients to the development of pseudocirrhosis through mechanisms that are not yet elucidated. Alternatively, this may be due to the fact that patients with HR+ disease tend to have longer survival and are on systemic therapy for longer periods of time, allowing more time for pseudocirrhosis to develop in response to systemic therapy,” Dr. Huppert said.

In future work, Dr. Huppert plans to examine a control arm of patients with liver disease who do not develop pseudocirrhosis to gain a better understanding of factors that might cause the condition. She also hopes to work with hepatologists to determine if new antifibrosis agents might be applicable to pseudocirrhosis. “There may be interesting things we can learn from other disease states and apply to this condition,” she said.

The researchers analyzed data from 120 patients with pseudocirrhosis. 82.5% of patients were HR+/HER2–, 11.7% were HR+/HER2+, 2.5% were HR–/HER2+, and 3.3% were triple negative. Liver metastases were present in all patients, and 82.5% had more than 15 liver lesions.

A total of 92.5% of patients had previously undergone chemotherapy before pseudocirrhosis was identified, and the median time to diagnosis of pseudocirrhosis after diagnosis of liver metastases was 18.7 months. 50% of patients with pseudocirrhosis had stable or responding disease. After pseudocirrhosis diagnosis, patients underwent a median of 1.0 additional lines of therapy, and the median overall survival following pseudocirrhosis diagnosis was 7.9 months. A total of 80.8% of patients went on to be diagnosed with ascites, 17.5% with esophageal varices, 21.7% with splenomegaly, 10.0% with gastrointestinal bleeding, and 9.2% with hepatic encephalopathy.

Patients with radiographic evidence of ascites survived an average of 42.8 months after metastatic breast cancer diagnosis, while those without ascites survived an average of 76.2 months (P < .001).

Specialty care was rare: Just 7.5% of patients received a GI/hepatology consultation.

Dr. Huppert has no relevant financial disclosures.

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.

A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the treatment not only reduces fractures long-term, but it may also improve overall survival and increase bone density.

The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.

“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.

Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.

ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.

The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.

The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.

Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).

There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.

Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).

In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.

“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.

A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.

A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the treatment not only reduces fractures long-term, but it may also improve overall survival and increase bone density.

The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.

“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.

Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.

ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.

The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.

The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.

Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).

There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.

Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).

In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.

“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.

A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.

A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the treatment not only reduces fractures long-term, but it may also improve overall survival and increase bone density.

The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.

“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.

Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.

ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.

The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.

The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.

Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).

There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.

Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).

In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.

“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.

A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.

Results of the KEYNOTE-522 clinical trial highlight the importance of neoadjuvant treatment with pembrolizumab for improving survival in patients with early triple negative breast cancer (TNBC).

The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.

KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.

The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.

A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.

The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.

At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.

Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.

Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.

The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).

“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.

The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.

Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).

“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.

In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.

The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.

Results of the KEYNOTE-522 clinical trial highlight the importance of neoadjuvant treatment with pembrolizumab for improving survival in patients with early triple negative breast cancer (TNBC).

The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.

KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.

The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.

A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.

The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.

At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.

Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.

Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.

The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).

“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.

The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.

Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).

“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.

In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.

The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.

Results of the KEYNOTE-522 clinical trial highlight the importance of neoadjuvant treatment with pembrolizumab for improving survival in patients with early triple negative breast cancer (TNBC).

The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.

KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.

The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.

A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.

The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.

At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.

Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.

Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.

The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).

“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.

The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.

Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).

“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.

In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.

The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

Results from a new phase IIb, 2x2 randomized, open-label trial (GeparSEPTO) showed no improvement in pathologic complete response (pCR) rates when the RANKL inhibitor denosumab was added to anthracycline/taxane-based neoadjuvant chemotherapy in the treatment of primary breast cancer. The study found that a weekly anthracycline/taxane-based neoadjuvant chemotherapy led to improved pCR compared to an every 3-week schedule both overall and in patients with triple-negative breast cancer (TNBC), though it was associated with greater toxicity.

“Currently, I do not see a place for antiosteolytic agents as part of the neoadjuvant therapy in breast cancer,” said lead author Sibylle Loibl, MD, PhD, who is a breast cancer researcher at Goethe (Germany) University. The researchers can’t exclude the possibility of a long-term benefit, and patients will be followed for disease-free and overall survival.

The disappointing result comes after previous studies of denosumab or bisphosphonates as additions to adjuvant therapy reduced metastases and increased survival in breast cancer, prompting optimism that the agents might improve pCR rates and improve survival rates in the neoadjuvant setting.

The failure may be because of the shorter treatment duration, and it’s possible that pCR is not the best endpoint to study for a drug that has long-acting potential, according to Dr. Loibl.

Patients were randomized to 120 mg denosumab every 4 weeks for six cycles or to receive no supplementary treatment. Patients with or without denosumab either received nab-paclitaxel 125 mg/m² weekly for 12 weeks or on days 1 and 8 every 3 weeks, over four cycles (eight total doses), then epirubicin/cyclophosphamide, 90/600 mg/m² (every 2 and 3 weeks, respectively). Patients with triple-negative breast cancer also received carboplatin. Patients with ERBB2-positive breast cancer received the trastuzumab biosimilar ABP980 plus pertuzumab.

The study included 780 patients (1 male), with a median age of 49.0 years. There was no difference in pCR among denosumab recipients and nonrecipients (41.0% versus 42.8%; P = .58). Weekly nab-paclitaxel led to a higher pCR rate than a schedule of days 1 and 8 every 3 weeks (44.9% versus 39.0%; P = .06, significance level of alpha = .10). Among subgroups, there was only a difference in pCR rates among those with TNBC (60.4% versus 50.0%; P = .06). Grade 3-4 toxic effects were similar regardless of denosumab exposure, but nonhematologic grade 3-4 toxicity was higher with weekly nab-paclitaxel (33.7% versus 24.1%; P = .004).

“The overall pCR difference (with nab-paclitaxel as neoadjuvant chemotherapy) seems small, but looking at the data from the GeparSEPTO study we would expect a transformation into a better invasive disease-free survival. Looking specifically into patients with TNBC, there is clear pCR increase by using the weekly regimen. With just over 60%, this is the highest pCR rate reported so far for a chemotherapy-only regimen. I would prefer to use nab-paclitaxel also in early breast cancer and would use the weekly regimen for women with TNBC who are at high risk,” Dr. Loibl said.

The study was limited by an imbalance of tumor subtypes between the treatment groups. The authors wrote that the results should guide further research, but nab-paclitaxel should not currently be viewed as a standard neoadjuvant treatment of breast cancer.

The study was funded by the German Breast Group, Bristol Myers Squibb, and Amgen. Dr. Loibl has served on the advisory boards or given lectures for AbbVie, Amgen, Bayer, Celgene, EirGenix, GSK, Lilly, Merck, Puma, Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Pierre Fabre, Prime/Medscape, Bristol Myers Squibb, Chugai, Ipsen, Roche, and Samsung. She also holds a related patent.

Results from a new phase IIb, 2x2 randomized, open-label trial (GeparSEPTO) showed no improvement in pathologic complete response (pCR) rates when the RANKL inhibitor denosumab was added to anthracycline/taxane-based neoadjuvant chemotherapy in the treatment of primary breast cancer. The study found that a weekly anthracycline/taxane-based neoadjuvant chemotherapy led to improved pCR compared to an every 3-week schedule both overall and in patients with triple-negative breast cancer (TNBC), though it was associated with greater toxicity.

“Currently, I do not see a place for antiosteolytic agents as part of the neoadjuvant therapy in breast cancer,” said lead author Sibylle Loibl, MD, PhD, who is a breast cancer researcher at Goethe (Germany) University. The researchers can’t exclude the possibility of a long-term benefit, and patients will be followed for disease-free and overall survival.

The disappointing result comes after previous studies of denosumab or bisphosphonates as additions to adjuvant therapy reduced metastases and increased survival in breast cancer, prompting optimism that the agents might improve pCR rates and improve survival rates in the neoadjuvant setting.

The failure may be because of the shorter treatment duration, and it’s possible that pCR is not the best endpoint to study for a drug that has long-acting potential, according to Dr. Loibl.

Patients were randomized to 120 mg denosumab every 4 weeks for six cycles or to receive no supplementary treatment. Patients with or without denosumab either received nab-paclitaxel 125 mg/m² weekly for 12 weeks or on days 1 and 8 every 3 weeks, over four cycles (eight total doses), then epirubicin/cyclophosphamide, 90/600 mg/m² (every 2 and 3 weeks, respectively). Patients with triple-negative breast cancer also received carboplatin. Patients with ERBB2-positive breast cancer received the trastuzumab biosimilar ABP980 plus pertuzumab.

The study included 780 patients (1 male), with a median age of 49.0 years. There was no difference in pCR among denosumab recipients and nonrecipients (41.0% versus 42.8%; P = .58). Weekly nab-paclitaxel led to a higher pCR rate than a schedule of days 1 and 8 every 3 weeks (44.9% versus 39.0%; P = .06, significance level of alpha = .10). Among subgroups, there was only a difference in pCR rates among those with TNBC (60.4% versus 50.0%; P = .06). Grade 3-4 toxic effects were similar regardless of denosumab exposure, but nonhematologic grade 3-4 toxicity was higher with weekly nab-paclitaxel (33.7% versus 24.1%; P = .004).

“The overall pCR difference (with nab-paclitaxel as neoadjuvant chemotherapy) seems small, but looking at the data from the GeparSEPTO study we would expect a transformation into a better invasive disease-free survival. Looking specifically into patients with TNBC, there is clear pCR increase by using the weekly regimen. With just over 60%, this is the highest pCR rate reported so far for a chemotherapy-only regimen. I would prefer to use nab-paclitaxel also in early breast cancer and would use the weekly regimen for women with TNBC who are at high risk,” Dr. Loibl said.

The study was limited by an imbalance of tumor subtypes between the treatment groups. The authors wrote that the results should guide further research, but nab-paclitaxel should not currently be viewed as a standard neoadjuvant treatment of breast cancer.

The study was funded by the German Breast Group, Bristol Myers Squibb, and Amgen. Dr. Loibl has served on the advisory boards or given lectures for AbbVie, Amgen, Bayer, Celgene, EirGenix, GSK, Lilly, Merck, Puma, Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Pierre Fabre, Prime/Medscape, Bristol Myers Squibb, Chugai, Ipsen, Roche, and Samsung. She also holds a related patent.

Results from a new phase IIb, 2x2 randomized, open-label trial (GeparSEPTO) showed no improvement in pathologic complete response (pCR) rates when the RANKL inhibitor denosumab was added to anthracycline/taxane-based neoadjuvant chemotherapy in the treatment of primary breast cancer. The study found that a weekly anthracycline/taxane-based neoadjuvant chemotherapy led to improved pCR compared to an every 3-week schedule both overall and in patients with triple-negative breast cancer (TNBC), though it was associated with greater toxicity.

“Currently, I do not see a place for antiosteolytic agents as part of the neoadjuvant therapy in breast cancer,” said lead author Sibylle Loibl, MD, PhD, who is a breast cancer researcher at Goethe (Germany) University. The researchers can’t exclude the possibility of a long-term benefit, and patients will be followed for disease-free and overall survival.

The disappointing result comes after previous studies of denosumab or bisphosphonates as additions to adjuvant therapy reduced metastases and increased survival in breast cancer, prompting optimism that the agents might improve pCR rates and improve survival rates in the neoadjuvant setting.

The failure may be because of the shorter treatment duration, and it’s possible that pCR is not the best endpoint to study for a drug that has long-acting potential, according to Dr. Loibl.

Patients were randomized to 120 mg denosumab every 4 weeks for six cycles or to receive no supplementary treatment. Patients with or without denosumab either received nab-paclitaxel 125 mg/m² weekly for 12 weeks or on days 1 and 8 every 3 weeks, over four cycles (eight total doses), then epirubicin/cyclophosphamide, 90/600 mg/m² (every 2 and 3 weeks, respectively). Patients with triple-negative breast cancer also received carboplatin. Patients with ERBB2-positive breast cancer received the trastuzumab biosimilar ABP980 plus pertuzumab.

The study included 780 patients (1 male), with a median age of 49.0 years. There was no difference in pCR among denosumab recipients and nonrecipients (41.0% versus 42.8%; P = .58). Weekly nab-paclitaxel led to a higher pCR rate than a schedule of days 1 and 8 every 3 weeks (44.9% versus 39.0%; P = .06, significance level of alpha = .10). Among subgroups, there was only a difference in pCR rates among those with TNBC (60.4% versus 50.0%; P = .06). Grade 3-4 toxic effects were similar regardless of denosumab exposure, but nonhematologic grade 3-4 toxicity was higher with weekly nab-paclitaxel (33.7% versus 24.1%; P = .004).

“The overall pCR difference (with nab-paclitaxel as neoadjuvant chemotherapy) seems small, but looking at the data from the GeparSEPTO study we would expect a transformation into a better invasive disease-free survival. Looking specifically into patients with TNBC, there is clear pCR increase by using the weekly regimen. With just over 60%, this is the highest pCR rate reported so far for a chemotherapy-only regimen. I would prefer to use nab-paclitaxel also in early breast cancer and would use the weekly regimen for women with TNBC who are at high risk,” Dr. Loibl said.

The study was limited by an imbalance of tumor subtypes between the treatment groups. The authors wrote that the results should guide further research, but nab-paclitaxel should not currently be viewed as a standard neoadjuvant treatment of breast cancer.

The study was funded by the German Breast Group, Bristol Myers Squibb, and Amgen. Dr. Loibl has served on the advisory boards or given lectures for AbbVie, Amgen, Bayer, Celgene, EirGenix, GSK, Lilly, Merck, Puma, Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Pierre Fabre, Prime/Medscape, Bristol Myers Squibb, Chugai, Ipsen, Roche, and Samsung. She also holds a related patent.

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

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

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

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

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

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

Time-restricted eating reduced cardiovascular risk among older breast cancer survivors, a single-group feasibility study suggests.

The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.

“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.

The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.

Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.

“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.

“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.

This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”

“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.

“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.

The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.

The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.

Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.

All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.

Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.

The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.

Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.

The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).

Other data showed that the average BMI remained the same (P = .10).

At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.

Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.

The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.

“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.

Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.

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

Time-restricted eating reduced cardiovascular risk among older breast cancer survivors, a single-group feasibility study suggests.

The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.

“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.

The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.

Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.

“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.

“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.

This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”

“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.

“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.

The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.

The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.

Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.

All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.

Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.

The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.

Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.

The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).

Other data showed that the average BMI remained the same (P = .10).

At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.

Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.

The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.

“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.

Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.

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

Time-restricted eating reduced cardiovascular risk among older breast cancer survivors, a single-group feasibility study suggests.

The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.

“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.

The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.

Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.

“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.

“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.

This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”

“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.

“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.

The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.

The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.

Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.

All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.

Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.

The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.

Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.

The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).

Other data showed that the average BMI remained the same (P = .10).

At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.

Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.

The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.

“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.

Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.

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