Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for XXXX : a randomised, double-blind, phase 3 study.

@entity1 @entity1501 @entity1149 @entity2186 @entity619 @entity1398 @entity204 @entity902
BACKGROUND: Several studies have shown the efficacy, tolerability, and ease of administration of pemetrexed-an antifolate antineoplastic agent-in @entity1 with advanced @entity1149 . We assessed pemetrexed as maintenance therapy in @entity1 with this disease. METHODS: This randomised double-blind study was undertaken in 83 centres in 20 countries. 663 @entity1 with stage IIIB or IV disease who had not progressed on four cycles of @entity902 -based chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500 mg/m(2), day 1) plus best supportive care (n=441) or placebo plus best supportive care (n=222) in 21-day cycles until disease progression. Treatment was randomised with the Simon and Pocock minimisation method. @entity1 and investigators were masked to treatment. All @entity1 received @entity2186 , @entity1501 , and @entity619 . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00102804. FINDINGS: All randomly assigned @entity1 were analysed. Pemetrexed significantly improved progression-free survival (4.3 months [95% CI 4.1-4.7] vs 2.6 months [1.7-2.8]; hazard ratio [HR] 0.50, 95% CI 0.42-0.61, p<0.0001) and overall survival (13.4 months [11.9-15.9] vs 10.6 months [8.7-12.0]; HR 0.79, 0.65-0.95, p=0.012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0.0001), specifically fatigue (22 [5%] vs one [1%], p=0.001) and @entity1398 (13 [3%] vs 0, p=0.006). No pemetrexed-related @entity204 occurred. Relatively fewer @entity1 in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%] vs 149 [67%]; p=0.0001). INTERPRETATION: Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in @entity1 with advanced @entity1149 . FUNDING: Eli Lilly.
