Bevacizumab in advanced breast cancer: an opportunity as second-line therapy?

Bevacizumab is approved for use as first-line therapy in advanced breast cancer according to pivotal ECOG 2,100 trial. Recently, Food and Drug Administration (FDA) voted unanimously against this licensed indication from the product’s labeling. This is because 2 other trials have been conducted (AVADO and RIBBON-1) and both have shown a statistically significant improvement in progression-free survival, although of a much smaller magnitude than was seen in E2100 study. After meta-analysing 2-s-line randomized bevacizumab trials that addressed a little bit different populations (a pure second-line population in RIBBON2 and an heavily pretreated [1–2 previous lines] population in Miller trial), we have discovered that overall response rate (relative risk 1.63; 95% CI 1.02–2.62; P = 0.04) and progression-free survival (hazard ratio 0.85; 95% CI 0.73–0.98; P = 0.03) were significantly increased with the addition of bevacizumab to chemotherapy. Despite both trials, the results are not significant in terms of duration of responses; however, bevacizumab appears not to increase the toxicity of chemotherapy (in particular febrile neutropenia). In conclusion, bevacizumab label in breast cancer could be reconsidered at least for second-line setting where a standard option does not exist, and a real difference in OS is unproven and unnecessary with any regimen in randomized trials.