SABCS 2015: Pathologic Complete Response to Presurgery Chemotherapy Improves Survival for Patients With Triple-Negative Breast Cancer
Patients with stage II or stage III triple-negative breast cancer who had a pathologic complete response (pCR) after presurgery chemotherapy had increased event-free and overall survival compared with those who had more than minimal residual invasive disease at surgery following presurgery chemotherapy, according to results from the randomized phase II CALGB/Alliance 40603 clinical trial presented by Sikov et al at the 2015 San Antonio Breast Cancer Symposium, held December 8–12 in San Antonio, Texas (Abstract S2-05).
Many patients with triple-negative breast cancer, especially those with breast tumors larger than 2 cm or evidence that the cancer has spread to lymph nodes in the axilla, receive neoadjuvant chemotherapy. Previously published results from the CALGB/Alliance 40603 clinical trial showed that adding carboplatin or bevacizumab (Avastin) to standard neoadjuvant chemotherapy increased the number of patients with stage II or stage III triple-negative breast cancer who had a pathologic complete response, meaning that they had no residual invasive cancer detectable in breast tissue and lymph nodes removed during surgery, explained William Sikov, MD, Associate Director of Clinical Research in the Program in Women’s Oncology at Women and Infants Hospital of Rhode Island, and Associate Professor of Medicine and Obstetrics and Gynecology at the Alpert Medical School of Brown University.
“Our new data show that patients on any arm of this study who had a [pathologic complete response] had far superior outcomes compared with those who did not have a [pathologic complete response],” said Dr. Sikov. “After 3 years of follow-up, only 9% of patients who had a [pathologic complete response] had developed a distant recurrence, and only 6% had died, compared to 27% and 25%, respectively, of patients who did not have a [pathologic complete response],” he noted.
“While this is important, our study was not sufficiently large to have the statistical power to determine whether adding carboplatin or bevacizumab to standard neoadjuvant chemotherapy improved event-free and overall survival,” continued Dr. Sikov. “On the basis of these results, at the present time, neither carboplatin nor bevacizumab should be considered part of the standard neoadjuvant chemotherapy regimen for stage II or III [triple-negative breast cancer].”
CALBG/Alliance 40603
The CALGB/Alliance 40603 clinical trial enrolled 443 patients with operable stage II or III triple-negative breast cancer. Patients were randomly assigned to standard neoadjuvant chemotherapy, standard neoadjuvant chemotherapy plus carboplatin, standard neoadjuvant chemotherapy plus bevacizumab, or standard neoadjuvant chemotherapy plus carboplatin and bevacizumab. Surgery was performed from 4 to 8 weeks after the completion of neoadjuvant treatment.
Dr. Sikov and colleagues found that at 3 years after starting the study treatment, patients who had no residual invasive cancer detected in either breast tissue or lymph nodes had a 70% reduced risk of disease recurrence and an 80% reduced risk of death compared with those who did not have a pathologic complete response in both the breast and lymph nodes.
Including both patients with minimal residual invasive disease in either the breast or lymph nodes, as defined by the Residual Cancer Burden method, and those who achieved a pathologic complete response in both the breast and lymph nodes did not significantly alter outcomes in the analysis; risk of disease recurrence was reduced by 71%, and risk of death was reduced by 79%.
Further Research Needed
No significant differences in event-free and overall survival were observed when the researchers evaluated whether adding carboplatin or bevacizumab to standard neoadjuvant chemotherapy affected these outcomes.
“In regard to whether there is a benefit to adding either carboplatin or bevacizumab to standard chemotherapy for stage II or III [triple-negative breast cancer], it is important to highlight that this is not a negative study. Rather, it is underpowered, meaning that it was not designed to be large enough to prove or disprove a benefit for either agent,” said Dr. Sikov.
“Our results need to be considered alongside data from prior and ongoing studies with these agents in [triple-negative breast cancer],” he continued. “Going forward, the question is whether we want to commit the additional patients and resources necessary to answer this question or instead focus our research efforts in [triple-negative breast cancer] on other opportunities to improve outcomes.”
This study was supported by the National Cancer Institute’s Cancer Therapy Evaluation Program, Genentech, and the Breast Cancer Research Foundation. Dr. Sikov declared no conflicts of interest.
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