Randomized Study of Maintenance Pemetrexed versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901

Abstract Background The role of maintenance therapy for malignant pleural mesothelioma (MPM) is unknown. We performed a randomized phase 2 trial to determine if continuation of pemetrexed after first-line pemetrexed and platinum would improve progression-free survival (PFS). Methods Eligible patients with unresectable MPM, without disease progression following 4-6 cycles of pemetrexed and platinum were randomized 1:1 to observation or continuation of pemetrexed until progression, stratified by number of cycles ( Results 72 patients were registered from December 2010 to June 2016. The study closed early after 53 patients were randomized; 49 eligible (22 on observation, and 27 on pemetrexed arms) were included in the analysis. Median PFS was 3 months (95% confidence intervals (CI): 2.6-11.9) on observation and 3.4 months (95% CI: 2.8-9.8) on pemetrexed (hazard ratio (HR) 0.99; 95% CI: 0.51-1.90; p=0.9733). Median overall survival (OS) was 11.8 months (95% CI: 9.3-28.7) for observation, and 16.3 months (95% CI: 10.5-26.0) for pemetrexed (HR 0.86; 95% CI: 0.44-1.71; p=0.6737). Grade 3 or 4 toxicities on the pemetrexed arm included anemia (8%), lymphopenia (8%), neutropenia (4%), and fatigue (4%). A higher baseline level of soluble mesothelin-related peptide was associated with worse PFS (HR 1.86, 95% CI: 1.00-3.46, p=0.049). Conclusion Maintenance pemetrexed following initial pemetrexed and platinum chemotherapy does not improve PFS in MPM patients.