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Addition of carboplatin, bevacizumab to neoadjuvant regimen increased response in triple-negative breast cancer
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The addition of carboplatin alone, bevacizumab alone or a combination of the two to neoadjuvant chemotherapy increased the rate of pathologic complete response among women with triple-negative breast cancer, according to results of a randomized, phase 2 trial.
Use of bevacizumab (Avastin, Genentech) was associated with more adverse events, results showed.
“If you have decided that a patient with triple-negative breast cancer should receive neoadjuvant chemotherapy based on the size of the tumor or their desire to improve their chance for breast conservation, our study suggests that you should consider adding carboplatin to the neoadjuvant regimen, and that you can do so with acceptable additional toxicities,” William M. Sikov, MD, FACP, associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, R.I., said during a press conference.
“[Bevacizumab] did increase the pathologic complete response rates, as well, but at the cost of significant toxicities, so I don’t think that it should be routinely added to neoadjuvant chemotherapy,” Sikov said.
The trial included 443 patients with operable stage II or stage III triple-negative breast cancer.
Researchers randomly assigned patients to one of four treatment arms: standard neoadjuvant chemotherapy alone (n=108); neoadjuvant chemotherapy plus carboplatin area under the curve (AUC) 6 every 3 weeks for four cycles (n=113); neoadjuvant chemotherapy plus bevacizumab 10 mg/kg every 2 weeks for nine doses (n=110); or neoadjuvant chemotherapy plus carboplatin and bevacizumab (n=112).
Surgery was performed 4 to 8 weeks after the conclusion of neoadjuvant treatment.
The study utilized a 2 x 2 factorial design to compare pathologic complete response (pCR) rates in the carboplatin arms to patients not assigned to receive carboplatin, and pCR rates in the bevacizumab arms to patients not assigned to receive bevacizumab.
At the time of surgery, 42% of patients assigned to standard neoadjuvant chemotherapy alone had no detectable cancer in the breast. That percentage increased to 50% among those assigned to neoadjuvant chemotherapy plus bevacizumab, 53% among those assigned to neoadjuvant chemotherapy plus carboplatin, and 67% among those assigned to neoadjuvant chemotherapy plus carboplatin and bevacizumab.
Researchers reported 39% of patients assigned to standard neoadjuvant chemotherapy had no detectable cancer in the breast or lymph nodes at the time of surgery. The percentage increased to 43% among those assigned to chemotherapy plus bevacizumab, 49% among those assigned to chemotherapy plus carboplatin, and 60% among those assigned to chemotherapy plus carboplatin and bevacizumab.
Results showed the addition of carboplatin significantly increased pCR rates in the breast (OR=1.76; P=.0018), and in the breast and axilla combined (OR=1.71; P=.0029). The addition of bevacizumab significantly increased pCR in the breast (OR=1.58; P=.0089). Treatment with bevacizumab also was associated with increased pCR in the breast and axilla combined (OR=1.36; P=.0570), but the difference was not statistically significant.
“While our results show increases in pathologic complete response 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,” Sikov said. “Although the study is not large enough to detect significant differences in these endpoints, we plan to follow patients for 10 years after their surgery to see if patient outcomes suggest long-term benefits from the investigational treatments.”
The addition of carboplatin to treatment regimens was associated with increased rates of neutropenia and thrombocytopenia.
The addition of bevacizumab was associated with increased rates of neutropenia, thrombocytopenia, febrile neutropenia, hypertension, bleeding and thrombosis. About 10% of patients who received bevacizumab developed high blood pressure, Sikov said.
Correlative studies are pending to try to identify markers that may predict response or resistance to the standard and investigational regimens, Sikov said.
For more information:
Sikov WM. Abstract #S5-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.
Disclosure: The study was funded by the NCI–CTEP, Genentech, the Breast Cancer Research Foundation and the American Recovery and Reinvestment Act of 2009. Sikov reports no relevant financial disclosures.
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Clifford A. Hudis, MD
This large, randomized, phase 2 trial evaluated bevacizumab and/or carboplatin in addition to paclitaxel in the preoperative treatment of patients with triple-negative breast cancer. We see an increase in response rates in the breast with each one of these interventions. What this does is point us in the direction of future clinical trials. In the end, when we make broad recommendations for these kinds of treatments, we need to be quoting DFS and OS benefits or proven surrogate benefits, and I think we’re on the cusp of that.
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