1218PD - EAST-LC: Randomized controlled phase III trial of S-1 versus docetaxel in patients with non-small-cell lung cancer who had received a platinum-base...

Date 09 October 2016
Event ESMO 2016 Congress
Session NSCLC, metastatic
Topics Anticancer agents
Non-Small Cell Lung Cancer
Therapy
Biological Therapy
Presenter Makoto Nishio
Citation Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383
Authors M. Nishio1, T.S.K. Mok2, K. Nakagawa3, N. Yamamoto4, Y. Shi5, L. Zhang6, S. Lu7, R. Soo8, J. Yang9, S. Morita10, S. Sugawara11, H. Nokihara12, T. Takahashi13, K. Goto14, J. Chang15, M. Maemondo16, Y. Ichinose17, Y. Cheng18, W. Lim19, T. Tamura20
  • 1Department Of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 2Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, Hong Kong/CN
  • 3Department Of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama/JP
  • 4Third Department Of Internal Medicine, Wakayama Medical University, Wakayama/JP
  • 5Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), 100021 - Beijing/CN
  • 6State Key Laboratory Of Oncology In South China, Sun Yat-sen University Cancer Center, Guangzhou/CN
  • 7Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai/CN
  • 8Cancer Institute, National University Cancer Institute, Singapore, Singapore/SG
  • 9Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 10Department Of Biomedical Statistics And Bioinformatics, Kyoto University-Graduate school of medicine, Kyoto/JP
  • 11Pulmonary Medicine, Sendai Kousei Hospital, 980-0873 - Sendai/JP
  • 12Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 13Division Of Thoracic Oncology, Shizuoka Cancer Center, Suntogun/JP
  • 14Department Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 15Medical Oncology, Cancer Hospital Shanghai Medical University, 200032 - Shanghai/CN
  • 16Respiratory Medicine, Miyagi Cancer Center, 981-1293 - Natori/JP
  • 17Clinical Research Institute, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 18Medical Oncology, Jilin Province Cancer Hospital, 130012 - Changchun/CN
  • 19Medical Oncology, National Cancer Center, Singapore/SG
  • 20Thoracic Center, St. Luke's International Hospital, 104-8560 - Tokyo/JP

Abstract

Background

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.

Methods

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 

Results

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.

Japan Non-Japan
DOC S-1 DOC S-1
No of Pt 359 361 211 216
MST(m) 12.6 13.4 12.1 10.8
HR (95%CI) 0.922 (0.789-1.079) 1.056 (0.854-1.307)
Interaction test P value 0.3374

Conclusions

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

JapicCTI-101155 http://www.clinicaltrials.jp/user/cteDetail.jsp

Legal entity responsible for the study

Taiho Pharmaceutical Co.,Ltd.

Funding

Taiho Pharmaceutical Co.,Ltd.

Disclosure

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.