A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma

Abstract

IntroductionMalignant mesothelioma (MM) cells express the vascular endothelial growth factor (VEGF) receptor, and VEGF protein expression is detected in a majority of human mesothelioma biopsy specimens. Bevacizumab is a recombinant humanized monoclonal antibody that blocks the binding of VEGF to its receptor. We evaluated the addition of bevacizumab to cisplatin and pemetrexed as first-line treatment in patients with advanced, unresectable MM. MethodsPreviously untreated MM patients with advanced, unresectable disease received cisplatin (75mg/m2), pemetrexed (500mg/m2), and bevacizumab (15mg/kg) intravenously every 21days for a maximum of 6cycles. Patients with responsive or stable disease received bevacizumab (15mg/kg) intravenously every 21days until progression or intolerance. The primary endpoint was progression-free survival rate at 6months. Results53 patients were enrolled at 4 centers; 52 were evaluable for this analysis. The progression-free survival rate at 6months was 56% and the median progression-free survival was 6.9months (95% confidence interval [CI], 5.3–7.8months). The partial response rate was 40% and 35% of patients had stable disease. Median overall survival was 14.8months (95% CI; 10.0–17.0months). Grade 3/4 toxicities included neutropenia in 11%, hypertension in 6%, and venous thromboembolism in 13% of patients. ConclusionThis trial evaluating the addition of bevacizumab to cisplatin and pemetrexed in patients with previously untreated, advanced MM failed to meet the primary endpoint of a 33% improvement in the progression-free survival rate at 6months compared with historical controls treated with cisplatin and pemetrexed alone.