Avastin May Benefit Basal-Like Breast Cancer Patients

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A study of women with triple-negative breast cancer (TNBC) has shown that women with the basal-like subtype of breast cancer had higher rates of pathologic complete response (pCR) with the addition of bevacizumab (Avastin) to neoadjuvant chemotherapy than did women with non–basal-like breast cancer. No difference in response was seen between the two subtypes for the addition of carboplatin.

These results were part of a subtype analysis of the CALGB/Alliance 40603 study and were presented at the 2014 San Antonio Breast Cancer Symposium, held December 9–13 in San Antonio, Texas, by William M. Sikov, MD, associate director of clinical research for the program in women’s oncology at Women and Infants Hospital and associate professor of medicine at Alpert Medical School of Brown University in Providence, Rhode Island.

Earlier this year, results of the initial study of 443 women published in the Journal of Clinical Oncology showed that the addition of carboplatin or bevacizumab to neoadjuvant chemotherapy in women with stage II to III TNBC increased rates of pCR. In the subtype analysis, Sikov and colleagues sought to identify subgroups of patients who were more or less likely to benefit from the addition of these therapies.

They classified patients as having basal-like breast cancer (87%) or non–basal-like breast cancer, and found no difference in the rate of pCR in the breast between the two groups (54% vs 52%).

Looking at patients with basal-like disease, the addition of carboplatin increased the pCR rate for breast (47% vs 61%; P = .014) and breast/axilla (43% vs 56%; P = .018) compared with neoadjuvant chemotherapy alone. However, the researchers found that response did not vary between patients with basal-like and non–basal-like disease.

Similarly, in patients with basal-like disease, the addition of bevacizumab increased the rate of response in breast (45% vs 64%; P = .0009) and breast/axilla (43% vs 57%; P = .014) compared with neoadjuvant chemotherapy alone. In contrast though, the addition of bevacizumab conferred a significant benefit on patients with basal-like disease compared with those with non–basal-like disease (P = .024).

The researchers also looked at five gene expression immune cell signatures-B-cell, CD8, T-cell, IgG, and general immune cell signatures-and found that high levels of expression of each correlated with higher pCR rates in all patients, and in those with basal-like disease only.

“However, there was no association between these signatures and greater pCR benefit from carboplatin or bevacizumab,” Sikov said.

Looking at other gene expression signatures, the researchers found that a high proliferation signature was predictive of pCR and of greater bevacizumab benefit in all patients. A low estrogen signature was predictive of pCR and of greater bevacizumab benefit in all patients and in those with basal-like disease.

“While these are interesting observations, I don’t think that our data will change clinical practice, for two reasons,” Sikov said. “First, we observed a much lower percentage of non–basal-like triple-negative cancers than we had anticipated based on prior reports. Second, while subtype may be predictive of response with the addition of bevacizumab, interest in the use of this agent in early-stage triple-negative breast cancer has diminished following disappointing results from a number of phase III studies.”

Reference

1. Sikov WM, Barry WT, Hoadley KA, et al. Impact of intrinsic subtype by PAM50 and other gene signatures on pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NACT) +/- carboplatin (Cb) or bevacizumab (Bev): CALGB 40603/150709 (Alliance). Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S4-05.