Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy
Nasser H. Hanna, Frances A. Shepherd, Frank V. Fossella, Jose R. Pereira, Filippo de Marinis, Joachim von Pawel, U. Gatzemeier, Thomas Chang Yao Tsao, Miklos Pless, Thomas Müller, Hong-Liang Lim, Christopher E. Desch, Klára Szondy, Radj Gervais, Shaharyar, Christian Manegold, Sofia Paul, Paolo Paoletti, Lawrence Einhorn, Paul A. Bunn
Abstract
PURPOSE To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. PATIENTS AND METHODS Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m 2 intravenously (IV) day 1 with vitamin B 12 , folic acid, and dexamethasone or docetaxel 75 mg/m 2 IV day 1 with dexamethasone every 21 days. The primary end point was overall survival. RESULTS Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance P = .105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months ( P = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% v 5.3%; P < .001), febrile neutropenia (12.7% v 1.9%; P < .001), neutropenia with infections (3.3% v 0.0%; P = .004), hospitalizations for neutropenic fever (13.4% v 1.5%; P < .001), hospitalizations due to other drug related adverse events (10.5% v 6.4%; P = .092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P < .001) and all grade alopecia (37.7% v 6.4%; P < .001) compared with patients receiving pemetrexed. CONCLUSION Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available.