Bevacizumab in HER2neu Negative Locally Recurrent and Metastatic Breast Cancer: The BHerN Review

Mary Ondinee U. Manalo, Mark Anthony E. Agana and Corazon A Ngelangel

Section of Medical Oncology, Department of Medicine, College of Medicine and
Philippine General Hospital, University of the Philippines Manila

Introduction. A promising strategy for HER2-negative metastatic breast cancer (mBC) is to target the vascular endothelial growth factor receptor using bevacizumab. Several randomized controlled trials (RCTs) have consistently demostrated improvement in progression-free survival (PFS).

Methods. This meta-analysis was undertaken to determine the added benefit of bevacizumab (BV) to chemotherapy in HER2-negative locally recurrent and mBC. RCTs that compared the efficacy and safety of BV+chemotherapy to placebo+chemotherapy in the first- or second-line setting were selected. The primary outcome was PFS. The secondary outcome measures were overall survival (OS) and objective response rate (ORR). Analysis of safety was done by pooling grades 3-5 toxicities. Four RCTs were included in the meta-analysis: E2100, AVADO, RIBBON-1, and RIBBON-2.

Results. The use of BV+chemotherapy showed statistically significant improvment in PFS (HR 0.73 [0.65, 0.82] 95% CI, p<0.0001); subgroup analysis of triple-negative breast cancer (TNBC) also showed statistically significant increase in PFS (HR 0.56 [0.47, 0.67] 95% CI, p<0.00001). The ORR was statistically significant with a risk ratio of 1.36 in favour of BV (p<0.00001). OS did not reach statistical significance (HR 0.85 [0.56, 1.27] 95% CI, p=0.42). Grades 3-5 toxicities were consistently higher in the BV arm with a risk ratio of 1.90 (p<0.00001).

Conclusion. BV prolongs PFS and increases ORR in patients with HER2-negative locally-recurrent and mBC. OS was comparable in both arms. Toxicities significantly increased with the addition of BV to chemotherapy, but fatal reactions were rare in all four trials. The addition of BV to conventional first- or second-line chemotherapy is justified in TN mBC since there is still no standard treatment for this.

Key Words: bevacizumab, HER2 negative, triple negative metastatic breast cancer