Bevacizumab-Docetaxel-Carboplatin Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer

Abstract & Commentary

By William B. Ershler, MD

Synopsis: In a single-arm, multicenter, Phase 2 trial, bevacizumab in combination with docetaxel and carboplatin achieved a pathological complete response in 19 of 45 patients with stage II/III triple-negative breast cancer. Forty-four of the 45 patients completed the planned six cycles and toxicity was manageable. One patient had delayed wound healing as a subsequent surgical complication. Thus, bevacizumab may provide significant improvement in neoadjuvant strategies for triple-negative breast cancer and further investigation is warranted.

Source: Kim HR, et al. Multicentre phase II trial of bevacizumab combined with docetaxel-carboplatin for the neoadjuvant treatment of triple-negative breast cancer (KCSG BR-0905). Ann Oncol 2013;24:1485-1490.

Optimal management of the 15-20%1 of patients whose breast cancer is characterized by the lack of expression of estrogen receptor (ER) and progesterone receptor, and the lack of human epidermal growth factor receptor 2 (HER2) overexpression and/or amplification is yet to be established.2 Although triple-negative breast cancer (TNBC) is generally considered more aggressive with limited disease-free intervals and shorter survival, it has been noted that if a pathological complete response is achieved by neoadjuvant treatment, overall survival is comparable to patients with non-TNBC. Thus, optimizing initial therapy is of paramount importance. Standard approaches include combinations of anthracyclines and taxanes,3,4 but there is some reason to believe that TNBC patients might be particularly sensitive to platinum analogues.5,6 Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), also has been shown to be active against TNBC7,8 and might be of added value to a platinum-based regimen in the neoadjuvant setting.

The current report describes a single-arm Phase 2 study conducted over a 14-month period (October 2010 to December 2011) at seven centers in Korea. Women (n = 45) with hormone receptor-negative and HER2-negative, stage II/III breast cancer received six cycles of docetaxel (75 mg/m2), carboplatin (AUC = 5), and bevacizumab (15 mg/kg) at 21-day intervals. The bevacizumab was eliminated from the sixth cycle so as not to interfere with surgical wound healing. The primary endpoint was pathological complete response (pCR) in breasts and axillary lymph nodes.

Of the 45 enrolled patients, 44 completed therapy and underwent surgery. The median age was 45 (range 30–72) years. Axillary lymph nodes were positive in 80% of patients (n = 36) at diagnosis. The pCR rate was 42% (n = 19); clinical response rate 96% (n = 43); complete 13% (n = 6); partial 82% (n = 37); stable disease 2% (n = 1). Breast-conserving surgery was undertaken in 78% of patients (n = 35). Most frequent grade 3/4 adverse events were neutropenia (84%, n = 38) and febrile neutropenia (9%, n = 4). One patient experienced delayed wound healing after surgery.

Commentary

Thus, neoadjuvant bevacizumab, docetaxel, and carboplatin resulted in an encouraging pCR rate. Certainly there remains room for improvement, but it appears from this study that the addition of bevacizumab provides a net gain in terms of achieving a pCR, and this with negligible wound healing problems after surgery. This latter point is notable because there have been concerns raised regarding bevacizumab-related postoperative wound complications reported by some.9 Perhaps not including the drug in the final cycle will minimize surgical complications, as suggested by this report.

The likely impact of added becaizumab in this setting still needs to be determined by a randomized clinical trial. In this regard, the community awaits results from the ongoing BEATRICE study, which examines bevacizumab added to standard antrhcycline/taxane in the adjuvant setting for TNBC patients. However, a TNBC-specific neoadjuvant trial utilizing a platinum/taxane +/- bevacizumab design remains on the “to-do” list.

References

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8. Thomssen C, et al. Oncology 2012;82:218-227.

9. Golshan M, et al. Ann Surg Oncol 2011;18:733-737.