A Randomized Phase 3 Trial Comparing Pemetrexed/Carboplatin and Docetaxel/Carboplatin as First-Line Treatment for Advanced, Nonsquamous Non-small Cell Lung Cancer

Introduction This study compared survival without toxicity in patients with advanced, nonsquamous non-small cell lung cancer who were treated with first-line pemetrexed/carboplatin or docetaxel/carboplatin. Methods This multicenter, open-label, parallel-group, phase 3 trial comprised patients randomized (1:1) to pemetrexed/carboplatin ( n = 128) or docetaxel/carboplatin ( n = 132). Patients received treatment on day 1 of each 21-day cycle (maximum of six cycles). Treatment included carboplatin (area under the curve=5 mg/ml × min) and pemetrexed (500 mg/m 2 ) or docetaxel (75 mg/m 2 ). The primary outcome measure, survival without treatment-emergent grade 3/4 toxicity, was defined as the time from randomization to the first treatment-emergent grade 3/4 adverse event or death and was analyzed using a log-rank test. The analysis population included 106 patients in the pemetrexed/carboplatin (Pem/Carb) group and 105 patients in the docetaxel/carboplatin (Doc/Carb) group. Results Survival without treatment-emergent grade 3/4 toxicity was significantly longer in the Pem/Carb versus the Doc/Carb group (log-rank p p = 0.934; median survival: 14.9 versus 14.7 months; adjusted hazard ratio=0.93 [95% confidence interval: 0.66–1.32]). Compared with the Doc/Carb group, fewer patients in the Pem/Carb group experienced grade 3/4 drug-related, treatment-emergent neutropenia, leukopenia, or febrile neutropenia, and more patients experienced anemia and thrombocytopenia. There were three study drug-related deaths during treatment in each group. Conclusions The favorable benefit-to-risk profile of pemetrexed/carboplatin suggests that pemetrexed/carboplatin is an appropriate first-line treatment option for chemonaive patients with advanced, nonsquamous non-small cell lung cancer.