Survival without common toxicity criteria grade 3/4 toxicity for pemetrexed compared with docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): A risk-benefit analysis

Background: In a recent large phase III study, previously treated patients with advanced non-small cell lung cancer who received pemetrexed demonstrated a survival time similar to patients who received docetaxel (median, 8.3 months with pemetrexed versus 7.9 months with docetaxel), with a more favorable toxicity profile, and significantly fewer Common Toxicity Criteria grade 3/4 toxicities. This is a retrospective risk-benefit analysis of survival without grade 3/4 toxicity, defined as the time to the first occurrence of Common Toxicity Criteria grade 3 or 4 toxicity or death, in the prospective phase III study comparing pemetrexed with docetaxel. Methods: A total of 541 patients (of 571 randomized) received either pemetrexed (500 mg/m(2) intravenously [IV]) supplemented with vitamin 13, injections and oral folic acid or docetaxel (75 mg/m(2) IV) on day 1 of 21-day cycles. Survival without grade 3/4 toxicity was analyzed using Kaplan-Meier and Cox methods. Results: Pemetrexed demonstrated a statistically significantly longer survival without grade 3/4 toxicity compared with docetaxel (hazard ratio = 0.60, 95% confidence interval: 0.50-0.72; p < 0.0001). A supportive analysis based on selected grade 3/4 toxicities (neutropenia lasting > 5 days, febrile neutropenia, infection with neutropenia, anemia, thrombocytopenia, fatigue, nausea, vomiting, diarrhea, stomatitis, and neurosensory events) also demonstrated an advantage for pemetrexed (hazard ratio = 0.53; 95% confidence interval: 0.44-0.64; p < 0.0001). Conclusion: This analysis of survival without grade 3/4 toxicity suggests a benefit-to-risk profile that favors pemetrexed over docetaxel in the second-line treatment of patients with non-small cell lung cancer.