Randomized phase 2 study of metronomic chemotherapy with or without bevacizumab for advanced breast cancer

Metronomic chemotherapy may target the tumor microvasculature. A randomized phase 2 trial at Dana-Farber Cancer Institute (Boston, MA) evaluated oral metronomic cyclophosphamide plus methotrexate (CM) chemotherapy with (n=34) or without (n=21) bevacizumab in patients with advanced breast cancer. The ORR was modestly higher in the CM-bevacizumab group than in the CM-only group (26% versus 10%); neither group met the 40% cutoff for further clinical evaluation. The median time to progression was 5.52 months with CM-bevacizumab versus 1.82 months with CM alone (p=0.008). The median overall survival was 29.6 months with CM-bevacizumab and 16.2 months with CM alone (p=0.7). The authors conclude that the combination of metronomic CM with bevacizumab significantly improved PFS over CM alone, although there was no statistically significant difference in OS.