S-1 Plus Cisplatin Versus Docetaxel Plus Cisplatin in Chemotherapy-Naive Patients with Advanced Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase III Study (TCOG0701)

Background Platinum-based chemotherapy has been a standard of care in patients with advanced non-small-cell lung cancer (NSCLC). S-1 plus cisplatin (SP) was shown good activity and tolerability in previous phase II trials. Docetaxel plus cisplatin (DP) is the only third-generation regimen that demonstrated statistically significant improvement of overall survival (OS) and quality of life (QOL), compared with a second-generation regimen, vindesine plus cisplatin, in patients with advanced NSCLC. Method This randomized phase III study compared the OS between SP and DP in patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions. Patients received 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 in SP arm, or docetaxel 60 mg/m2 on day 1 plus cisplatin 80 mg/m2 on day 1 every 3 weeks in DP arm, both up to six cycles. The non-inferiority study design was employed as upper confidence interval (CI) limit for HR Results From April 2007 to December 2008, 608 patients from 66 sites in Japan were randomized to SP (n = 303) or DP (n = 305). Patient demographics were well balanced between the two arms. Two interim analyses were preplanned. At the final analysis, a total of 480 death events were observed. OS for SP was non-inferior to DP (median survival, 16.1 versus 17.1 months, respectively; HR = 1.013; 96.4% CI, 0.837–1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. Statistically significantly lower rate of febrile neutropenia (7.4% versus 1.0%), grade 3/4 neutropenia (73.4% versus 22.9%), grade 3/4 infection (14.5% versus 5.3%), grade 1/2 alopecia (59.3% versus 12.3%) were observed in the SP arm than in the DP arm. QOL data investigated by EORTC QLQ-C30 and LC-13 favored for the SP arm. Conclusion S-1 plus cisplatin is a standard first-line chemotherapy regimen for advanced NSCLC.