Bevacizumab - In first-line treatment of advanced and/or metastatic renal cell carcinoma

Bevacizumab, an anti-vascular endothelial growth factor recombinant humanized monoclonal antibody, directly inhibits tumor angiogenesis and hence tumor growth. First-line therapy with intravenous bevacizumab 10 mg/kg every 2 weeks plus subcutaneous interferon-alpha-2a 9 million international units three times weekly has been evaluated in two randomized, double-blind or open-label, multicenter phase III trials (AVOREN [n = 649] and CALGB 90206 [n = 732]). Bevacizumab combination therapy resulted in a median progression-free survival that was significantly (p <= 0.0001) longer than that seen with placebo plus interferon-a-2a in AVOREN (10.2 vs 5.4 months) [hazard ratio (HR) 0.63 (95% CI 0.52, 0.75)] and that seen with interferon-alpha-2a alone in CALGB 90206 (8.5 vs 5.2 months). Overall survival data in AVOREN and CALGB 90206 are not yet mature. In the interim overall survival analysis in AVOREN, median overall survival was 19.8 months with placebo plus interferon-a-2a, but had not yet been reached with bevacizumab plus interferon-alpha-2a (FIR 0.79 [95% CI 0.62, 1.02; p = 0.0670]). The overall tumor response rate with bevacizumab plus interferon-alpha-2a was significantly (p <= 0.0001) higher than with placebo plus interferon-alpha-2a in AVOREN (31% vs 13%) and that with interferon-alpha-2a alone in CALGB 90206 (25.5% vs 13.1%). Subgroup analyses in AVOREN suggested that interferon-alpha-2a dose reductions (to manage grade 3 adverse events attributable to the drug) did not compromise the efficacy of combination treatment with bevacizumab plus interferon-alpha-2a. The addition of bevacizumab to interferon-a-2a in AVOREN was generally well tolerated. No unexpected/new adverse events were observed; bevacizumab-associated toxicities were generally of mild intensity.