Miller KD, et al. - Researchers assessed how bevacizumab influences the outcomes in the adjuvant setting in patients with human epidermal growth factor receptor 2–negative breast cancer in E5103 trial. They found no improvement in invasive disease–free survival (IDFS) or overall survival resulted from incorporation of bevacizumab into sequential anthracycline- and taxane-containing adjuvant therapy in patients with high-risk human epidermal growth factor receptor 2–negative breast cancer. Given that, the rate of early discontinuation were high, therefore, longer duration bevacizumab therapy was unlikely to be feasible.

Methods

• Three patient arms received (1:2:2) placebo with doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (arm A), bevacizumab only during AC and paclitaxel (arm B), or bevacizumab during AC and paclitaxel followed by bevacizumab monotherapy for 10 cycles (arm C).
• This trial involved random assignment stratification and bevacizumab dose adjustment for choice of AC schedule.
• Concurrent administration of radiation and hormonal therapy with bevacizumab in arm C was carried out.
• Invasive disease–free survival (IDFS) was primary end point.

Results

• A total of 4,994 patients were enrolled, with median age 52 years; 64% were estrogen receptor positive, 27% were lymph node negative, and 78% received dose-dense AC.
• Across all arms, the observed chemotherapy-related adverse events including myelosuppression and neuropathy were similar.
• Bevacizumab-treated patients more commonly experienced grade ≥ 3 hypertension, but thrombosis, proteinuria, and hemorrhage were not that common.
• Data showed that, the cumulative incidence of clinical congestive heart failure at 15 months was 1.0%, 1.9%, and 3.0% in arms A, B, and C, respectively.
• Less than anticipated bevacizumab exposure was reported, with approximately 24% of patients in arm B and approximately 55% of patients in arm C discontinuing bevacizumab before completing planned therapy.
• Findings revealed that, 5-year IDFS was 77% (95% CI, 71% to 81%) in arm A, 76% (95% CI, 72% to 80%) in arm B, and 80% (95% CI, 77% to 83%) in arm C.