Published in:
01-03-2008 | Adis Drug Profile
Bevacizumab
In First-Line Treatment of Advanced and/or Metastatic Renal Cell Carcinoma
Published in: BioDrugs | Issue 2/2008
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▴ 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-α-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-α-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-α-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-α-2a, but had not yet been reached with bevacizumab plus interferon-α-2a (HR 0.79 [95% CI 0.62, 1.02; p = 0.0670]).
▴ The overall tumor response rate with bevacizumab plus interferon-α-2a was significantly (p ≤ 0.0001) higher than with placebo plus interferon-α-2a in AVOREN (31% vs 13%) and that with interferon-α-2a alone in CALGB 90206 (25.5% vs 13.1%).
▴ Subgroup analyses in AVOREN suggested that interferon-α-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-α-2a.
▴ The addition of bevacizumab to interferon-α-2a in AVOREN was generally well tolerated. No unexpected/new adverse events were observed; bevacizumab-associated toxicities were generally of mild intensity.