Bevacizumab plus paclitaxel can slow breast cancer progression but does not improve overall survival

Adding bevacizumab to treatment with paclitaxel does not prolong overall survival among patients with metastatic breast cancer; however, the combination therapy is associated with a significant improvement in progression-free survival, according to the results of a trial published in the New England Journal of Medicine (NEJM).

Bevacizumab was recently approved for use in combination with paclitaxel for the treatment of chemotherapy-näive patients with metastatic HER2-negative breast cancer.

This open-label, randomized, controlled study included 722 patients with histologically or cytologically confirmed metastatic breast cancer (predominantly HER2-negative) who had not previously received cytotoxic therapy for their metastatic disease. Patients were randomized to receive paclitaxel 90 mg/m² of body surface area on Days 1, 8, and 15 every 4 weeks, either alone or with intravenous (IV) bevacizumab 10 mg/kg of body weight on Days 1 and 15. The primary end point was progression-free survival, defined as the time from randomization to disease progression or all-cause death. Secondary end points included objective response rate, overall survival, quality of life, and adverse drug events.

A total of 624 patients demonstrated progression-free survival. The combination therapy was associated with significantly longer progression-free survival compared with paclitaxel alone (median, 11.8 mo vs 5.9 mo; HR for progression=0.60; 95% CI, 0.51–0.70; P<.001); bevacizumab plus paclitaxel was also associated with a significantly improved objective response rate compared with paclitaxel monotherapy (36.9% vs 21.2%; P<.001). These benefits of adjunctive bevacizumab were demonstrated to decline over time (P<.001). Although bevacizumab plus paclitaxel increased the survival rate at 1 year compared with paclitaxel alone (81.2% vs 73.4%; P=.01), the median overall survival rates were similar (26.7 mo vs 25.2 mo; HR for overall survival=0.88; P=.16). The combination therapy was not demonstrated to significantly improve or hinder the patients’ quality of life versus paclitaxel alone, as assessed by the validated FACT breast cancer-specific questionnaire.

Bevacizumab plus paclitaxel was associated with a greater incidence of several grade 3 or 4 adverse drug events compared with paclitaxel alone, including hypertension, proteinuria, headache, and cerebrovascular ischemia. Overall, most adverse events were minimal, did not negatively affect quality of life, and rarely limited therapy.

Source

Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer.

N Engl J Med

. 2007;357:2666–2676.