Two phase II studies had evaluated the efficacy and safety of S-1, an oral 5-FU, in patients with previously treated NSCLC. The results of these studies suggested that S-1 was comparable to the docetaxel (DOC), a standard therapy for previously treated NSCLC. This randomized phase III study aims to establish non-inferiority of S-1 monotherapy to DOC in patients with previously treated NSCLC in Asia.
Patients with stage IIIB/IV NSCLC who had received at least 1 regimen of platinum-based chemotherapy with/without prior exposure to gefitinib or erlotinib were eligible. Patients were randomized to S-1 (80-120 mg/day on days 1-28 every 42-day) or DOC (60 mg/m2 in Japan, 75 mg/m2 in other countries, on day 1 every 21days). The primary objective was to evaluate whether S-1 is non-inferior to DOC in terms of overall survival (OS) (upper CI limit for HR
Total of 1154 patients were enrolled from 7/2010 to 6/2014; and median follow-up time was 30.75 months. The median OS of the S-1 group was non-inferior to the DOC group (12.75 months versus 12.52 months; hazard ratio [HR] 0.945; 95% confidence interval [CI] 0.833-1.073; P =0.3818). Subgroup analysis by country (Japan vs non-Japan) is summarized in Table. PFS was also similar between the two groups (2.86 months versus 2.89 months). Grade 3 or higher febrile neutropenia and neutropenia were higher in the DOC group (0.9%vs 13.6%; 5.4% vs 47.7% in S1 and DOC group, respective). Other non-hematoloic toxicities in S1 and DOC group are as followed; diarrhea (37.2% versus 18.2%), stomatitis (23.9% versus 14.5%) and decreased appetite (52.6% versus 37.9%), respectively.
|No of Pt||359||361||211||216|
|Interaction test P value||0.3374|
S-1 is non-inferior to DOC in terms of OS, with tolerable toxicity. S-1 monotherapy is one of the treatment options for patients with previously treated NSCLC.
Clinical trial identification
Legal entity responsible for the study
Taiho Pharmaceutical Co.,Ltd.
Taiho Pharmaceutical Co.,Ltd.
M. Nishio: Honori: Pfizer,BMS, ONO, Chugai, Eli Lilly, TAIHO, AstraZeneca Daiichi Sankyo, Novartis Cooperate. Sponsored research for: Novartis, ONO, Chugai, Bristol-Myers Squibb, Taiho, Eli Lilly, Pfizer, Astellas, AstraZeneca. T.S.K. Mok: Stock ownership: Sanomics Advisory board:AZ, Roche/Genentech, Pfizer, Eli-Lilly, BI, Merck Serono, MSD, Janssen, Clovis, BioMarin, GSK, Novartis, SFJ, ACEA, Inc., Vertex, BMS. Sponsored research: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis, BMS. L. Zhang: Advisory board for Boehringer Ingelheim, Astrazeneca, BMS Cooperate. Sponsored research for Pfizer, Astrazeneca, BMS. R. Soo: Advisory board for Astra-Zeneca, Boehringer Ingelheim, Merck, Novartis, Pfizer, Roche, Taiho Honorarium for Astra-Zeneca, Boehringer Ingelheim, Lilly, Merck, Novartis, Pfizer, Roche, Taiho. J. Yang: Advisory board for Boehringer, Eli-Lilly, Bayer, Roche/Genentech/Chugai, Astrazeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, innopharma, Merrimack. S. Morita, S. Sugawara, T. Tamura: Honorarium for Taiho. H. Nokihara: Cooperate – sponsored research for Merck Serono, Pfizer, Taiho, Eisai, Chugai, Eli Lilly, Novartis, Daiichi Sankyo, GSK, Yakult, Quintiles, Astellas, AZ, BI, Ono Honorarium for Boehringer, Taiho, AZ, Ono, Sanofi, Eli Lilly. T. Takahashi: Cooperate – sponsored research for AstraZeneca, Eli Lilly, Chugai, ONO, Pfizer,Takeda.Taiho, MSD Honorarium for AstraZeneca, Eli Lilly, Chugai, ONO, Boehringer. K. Goto: Cooperate – sponsored research for Taiho, MSD, Astra Zeneka, Chugai, Nippon, BI, Ono, Quintiles, GSK, OxOnc, Pfizer, Kyowa Hakko Kirin, Eli Lilly, Yakult, Sumitomo Dainippon, Takeda, Novartis, DAIICHI SANKYO, Astellas, Eisai, Amgen, BMS. Y. Ichinose: Cooperate – sponsored research for Takeda, Nippon Kayaku Honorarium for Chugai, Kyowa Hakko Kirin, Taiho, Taisho Toyama. All other authors have declared no conflicts of interest.