pCR may obviate need for adjuvant chemotherapy

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.