(ChemotherapyAdvisor) – Adding bevacizumab to docetaxel and prednisone for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) did not improve overall survival and was associated with greater toxicity, despite an improvement in progression-free survival and objective response, investigators reported in the Journal of Clinical Oncology online March 26.

The Cancer and Leukemia Group B 90401 Phase 3 double-blind trial randomly assigned 1,050 patients with chemotherapy-naive progressive mCRPC to docetaxel 75mg/m2 IV over one hour for 21 days plus prednisone 5mg orally twice daily with either bevacizumab 15mg/kg IV every three weeks or placebo.

Median overall survival, the primary end point, was 22.6 months in the arm that received bevacizumab vs. 21.5 months for patients treated with placebo (HR, 0.91). Median progression-free survival was superior in the bevacizumab arm, 9.9 vs. 7.5 months, as was the proportion of patients with objective response, 49.4% vs. 35.5%. In the bevacizumab arm, ≥grade 3 treatment-related toxicity was more common, 75.4% vs. 56.2%, and there were more treatment-related deaths, 4.0% vs. 1.2%.

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The investigators noted these results failed to support the trial’s hypothesis, which was that inhibiting VEGF by adding bevacizumab to docetaxel and prednisone would provide a survival advantage to patients with mCRPC. This study further illustrates that success of future Phase 3 programs “is dependent on identifying critical biomarkers that enrich the study population for the targeted therapy and to better understand the associations between progression-free survival, prostate specific antigen response, and objective tumor response as an intermediate marker for overall survival.”