Survival without toxicity for cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemonaive patients with advanced non-small cell lung cancer: A risk-benefit analysis of a large phase III study

WOS: 000270645700017PubMed ID: 19473833Background: In a large phase III study, cisplatin and pemetrexed had non-inferior efficacy and better tolerability compared with cisplatin and gemcitabine in chemonaive patients with non-small cell lung cancer (NSCLC). The current analysis characterised the clinical benefit (i.e. survival) relative to clinical risk (i.e. drug-related toxicity) of the doublets. Patients and methods: A total of 1669 patients (of 1725 randomised) received 500 mg/m(2) pemetrexed IV followed by 75 mg/m(2) cisplatin IV on day 1 or gemcitabine 1250 mg/m(2) on days 1 and 8 and 75 mg/m(2) cisplatin on day 1, administered every 3 weeks for up to 6 cycles. Survival without toxicity (i.e. clinical benefit to risk) was defined as the time from randomisation to the first occurrence of any grade 3 or 4 drug-related toxicity or death, and was analysed using Kaplan-Meier and Cox methods. Results: In the overall patient population, survival without grade 3 or 4 drug-related toxicity was significantly longer for patients treated with cisplatin and pemetrexed versus cisplatin and gemcitabine (HR = 0.70; P < 0.001), as was survival without grade 4 drug-related toxicity (HR = 0.83; P < 0.001). For patients with non-squamous NSCLC, survival without toxicity with cisplatin and pemetrexed was superior to cisplatin and gemcitabine for grade 3 or 4 drug-related toxicity (HR = 0.64; P < 0.001) and for grade 4 drug-related toxicity (HR = 0.77; P < 0.001), whereas no treatment-arm difference was observed in the squamous subgroup. Conclusions: Patients with non-squamous NSCLC treated with front-line cisplatin and pemetrexed have superior survival without toxicity (i.e. clinical benefit-to-risk profile) compared with patients treated with cisplatin and gemcitabine. (C) 2009 Elsevier Ltd. All rights reserved.Eli Lilly and CompanyEli LillyThe study was sponsored and funded by Eli Lilly and Company. As the sponsor, Eli Lilly was involved in the study design, in the collection, analysis and interpretation of the data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The authors would like to thank all the patients for their participation in this study. They would also like to thank Mary Alice Miller Ph.D., Noelle Gasco and Donna Miller from Eli Lilly and Company for their writing, editorial and administrative assistance, respectivel