Randomized Phase III Trial of S-1 Plus Cisplatin Versus Docetaxel Plus Cisplatin for Advanced Non-Small-Cell Lung Cancer (TCOG0701)

Background Quality of life (QOL) should be an explicit priority throughout the course of care for patients with advanced non-small-cell lung cancer (NSCLC). Docetaxel plus cisplatin (DP) is the only third-generation regimen that has demonstrated statistically significant improvements in overall survival and QOL by a head-to-head comparison with a second-generation regimen (vindesine plus cisplatin) in patients with advanced NSCLC. S-1 plus cisplatin (SP) has shown activity and good tolerability in phase II settings. Method Patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions were randomly assigned to receive either oral S-1 80 mg/m2/day (40 mg/m2 b.i.d.) on days 1 to 21 plus cisplatin 60 mg/m2 on day 8 every 5 weeks or docetaxel 60 mg/m2 on day 1 plus cisplatin 80 mg/m2 on day 1 every 3 weeks, both up to 6 cycles. The primary endpoint was overall survival (OS). A non-inferiority study design was employed; the upper confidence interval (CI) limit of the hazard ratio (HR) was Results From April 2007 through December 2008, 608 patients were randomly assigned to SP (n = 303) or DP (n = 305) at 66 sites in Japan. Patient demographics were well balanced between the two groups. Two interim analyses were preplanned. At the final analysis, a total of 480 deaths had occurred. The primary endpoint was met. OS in the SP arm was non-inferior to that in the DP arm (median survival, 16.1 vs. 17.1 months, respectively; HR = 1.013; 96.4% confidence interval, 0.837-1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. The rates of febrile neutropenia (7.4% vs. 1.0%), grade 3/4 neutropenia (73.4% vs. 22.9%), grade 3/4 infection (14.5% vs. 5.3%), and grade 1/2 alopecia (59.3% vs. 12.3%) were significantly lower in the SP arm than in the DP arm. In terms of physical functioning and global functioning on the EORTC QLQ-C30 and lung cancer module (LC-13), QOL was worse in the DP arm (repeated measures ANOVA: p Conclusion S-1 plus cisplatin is a standard first-line chemotherapeutic regimen for advanced NSCLC. Disclosure M. Nishio: HONORARIA: Chugai Pharma. K. Kobayashi: HONORARIA: a reasonal payment for lectuture speech from Taiho Pharmaceutical Company. M. Takeuchi: CONSULTANT OR ADVISORY ROLE; Taiho. All other authors have declared no conflicts of interest.