Neoadjuvant Carboplatin, Bevacizumab Improve pCR Rates in TNBC
SAN ANTONIO—Despite serious adverse events, adding carboplatin or bevacizumab to standard anthracycline- and taxane-based neoadjuvant chemotherapy (NAC), either individually or in combination, improves pathologic complete response (pCR) rates among women with triple-negative breast cancer (TNBC), according to authors of a randomized phase 2 clinical trial presented at the 2013 San Antonio Breast Cancer Symposium.
“We are excited to report that adding either therapy significantly increased the percentage of patients in whom cancer was eliminated in the breast, and that adding both was even more effective,” reported William M. Sikov, MD, FACP, associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, RI.
“For carboplatin, these results are very encouraging,” he said. “I think if you've decided a patient with triple-negative breast cancer should receive neoadjuvant chemotherapy, it makes sense to add carboplatin to your neoadjuvant regimen.”
While the results show increases in pCR rates with both carboplatin and bevacizumab, “we do not yet know how large an impact, if any, these differences will have on cancer recurrences or deaths,” Dr. Sikov cautioned. “Our supposition is that patients with pCR are more likely to survive.”
The phase 2 CALGB/Alliance 40603 trial (NCT00861705) was conducted by the Cancer and Leukemia Group B, now a member of the Alliance for Clinical Trials in Oncology. A total of 454 women with operable stage 2 or 3 TNBC were randomly assigned to receive standard neoadjuvant paclitaxel (80 mg/m2 weekly for 12 weeks) chemotherapy, including doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2); or standard neoadjuvant therapy plus carboplatin (area under the curve 6) every 3 weeks for four cycles during paclitaxel therapy; or standard neoadjuvant therapy plus bevacizumab (10 mg/kg every 2 weeks for nine cycles); or standard neoadjuvant therapy plus both carboplatin and bevacizumab.
Preliminary pCR outcomes for the first 369 patients “suggest that adding carboplatin or bevacizumab to standard NAC significantly increases pCR rates in stage 2 to 3 TNBC,” Dr. Sikov concluded.
pCR in breast tissue with or without neoadjuvant carboplatin was 60% versus 46% (odds ratio [OR], 1.76; P = 0.0018); in the bevacizumab arm, pCR was 59% compared with 48% in the no-bevacizumab arm (OR, 1.58; P = 0.0089).
pCR improvements associated with the two agents were additive rather than synergistic, Dr. Sikov noted.
Carboplatin was associated with “more problems of low blood counts” and missed, delayed, or reduced chemotherapy doses, Dr. Sikov noted. Grade 3/4 toxicities that were more common with carboplatin included neutropenia (56% vs. 20% of patients not receiving carboplatin) and thrombocytopenia (22% vs. 4%).
Bevacizumab was associated with high blood pressure (grade 3 hypertension, 11% vs. < 1%), blood clotting, bleeding and infections, as well as delayed postsurgical wound healing (4% vs. 1% without bevacizumab), Dr. Sikov reported.
“Bevacizumab was discontinued in 23% of assigned patients,” Dr. Sikov noted.
Patients receiving both carboplatin and bevacizumab also experienced a higher rate of neutropenia (19% vs. 7%) than controls.
Funding for the study included support from the National Institute of Health, Genentech and the Breast Cancer Research Foundation.
- Sikov WM et al. S5-01. Presented at: San Antonio Breast Cancer Symposium 2013. Dec. 10-14, 2013; San Antonio.