Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy.

Abstract

To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. 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/m² intravenously (IV) day 1 with vitamin B₁₂, folic acid, and dexamethasone or docetaxel 75 mg/m² IV day 1 with dexamethasone every 21 days. The primary end point was overall survival. Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance <i>P</i> = .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 (<i>P</i> = 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% <i>v</i> 5.3%; <i>P</i> < .001), febrile neutropenia (12.7% <i>v</i> 1.9%; <i>P</i> < .001), neutropenia with infections (3.3% <i>v</i> 0.0%; <i>P</i> = .004), hospitalizations for neutropenic fever (13.4% <i>v</i> 1.5%; <i>P</i> < .001), hospitalizations due to other drug related adverse events (10.5% <i>v</i> 6.4%; <i>P</i> = .092), use of granulocyte colony-stimulating factor support (19.2% <i>v</i> 2.6%, <i>P</i> < .001) and all grade alopecia (37.7% <i>v</i> 6.4%; <i>P</i> < .001) compared with patients receiving pemetrexed. 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.