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

Introduction: Malignant 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. Methods: Previously 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. Results: 53 patients were enrolled at 4 centers; 52 were evaluable for this analysis. The progression-free survival rate at 6. months was 56% and the median progression-free survival was 6.9. months (95% confidence interval [CI], 5.3-7.8. months). The partial response rate was 40% and 35% of patients had stable disease. Median overall survival was 14.8. months (95% CI; 10.0-17.0. months). Grade 3/4 toxicities included neutropenia in 11%, hypertension in 6%, and venous thromboembolism in 13% of patients. Conclusion: This 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 6. months compared with historical controls treated with cisplatin and pemetrexed alone.