625P - Randomized phase II study of S-1 plus oral leucovorin (SL) versus SL plus oxaliplatin (SOL) versus S-1 plus cisplatin (SP) in patients with advance...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Gastric Cancer
Presenter Kensei Yamaguchi
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors K. Yamaguchi1, S. Hironaka2, N. Sugimoto3, T. Moriwaki4, Y. Komatsu5, T. Nishina6, A. Tsuji7, T.E. Nakajima8, M. Gotoh9, N. Machida10, N. Fuse11, T. Esaki12, Y. Emi13, Y. Takinishi14, S. Matsumoto15, N. Boku16, H. Baba17, I. Hyodo18
  • 1Division Of Gastroenterology, Saitama Cancer Center, 362-0806 - Saitama/JP
  • 2Clinical Trial Promotion Department, Chiba Cancer Center, 260-8717 - Chiba/JP
  • 3Department Of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka/JP
  • 4Division Of Gastroenterology, University of Tsukuba, 305-8577 - Tsukuba/JP
  • 5Department Of Cancer Center, Hokkaido University Hospital, Sapporo/JP
  • 6Department Of Gastroenterology, National Hospital Organization Shikoku Cancer Center, Ehime/JP
  • 7Department Of Medical Oncology, Kobe City Medical Center General Hospital, 650-0047 - Hyogo/JP
  • 8Department Of Clinical Oncology, St. Marianna University School of Medicine, Kanagawa/JP
  • 9Internal Medicine Ii, Osaka Medical College, JP-569-8686 - Takatsuki/JP
  • 10Division Of Gastrointestinal Oncology, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 11Division Of Gastrointestinal Oncology And Digestive Endscopy, National Cancer Center Hospital East, Chiba/JP
  • 12Department Of Gastrointestinal And Medical Oncology, National Kyusyu Cancer Center, Fukuoka/JP
  • 13Department Of Surgery, Saiseikai Fukuoka General Hospital, 810-0001 - Fukuoka/JP
  • 14Department Of Internal Medicine, Showa University Northern Yokohama Hospital, Kanagawa/JP
  • 15Department Of Therapeutic Oncology, Kyoto University-Graduate school of medicine, Kyoto/JP
  • 16Department Of Clinical Oncology, St. Marianna University School of Medicine, 216-8511 - Kanagawa/JP
  • 17Department Of Gastroenterological Surgery, Kumamoto University, JP-860-8556 - Kumamoto/JP
  • 18Dividion Of Gastroenterology, University of Tsukuba, Tsukuba/JP

Abstract

Aim

We have investigated the enhanced antitumor activity by oral leucovorin (LV) when added to S-1, and found optimized treatment schedule of S-1 plus LV (SL), 1 week (w) on and 1w off, as a platform regimen. In this treatment schedule, SL showed promising efficacy in previous phase II trials of colorectal and pancreatic cancer. Here, we evaluated the efficacy and the safety of SL and SL plus oxaliplatin (SOL) compared with S-1 plus cisplatin (SP) as a reference standard treatment in advanced gastric cancer (AGC).

Methods

Patients who were previously untreated with chemotherapy for AGC were randomized equally to receive SL (S-1; 40-60 mg bid and oral LV; 25 mg bid for 1w, q2w), SOL (SL plus oxaliplatin; 85 mg/m2 on day 1, q2w), or SP (S-1; 40-60 mg bid for 3w and cisplatin; 60 mg/m2 on day 8, q5w). The primary endpoint was response rate (RR) by the independent review committee. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Clinical trial registration: JapicCTI-111635.

Results

From Oct 2011 to Dec 2012, 145 patients were randomized, and 142 were included in the efficacy analysis (SL/SOL/SP, 47/47/48). The confirmed RR (%) of SL/SOL/SP was 43 (95% Cl: 28-58)/ 66 (51-79)/ 46 (31-61) (SL vs. SP, p = 0.837; and SOL vs. SP, p = 0.063). DCR (%) was 74/100/83 (SL vs. SP, p = 0.324; and SOL vs. SP, p = 0.0057). Median PFS was 4.2/8.3/5.6 months (SL vs. SP, HR = 1.08, p = 0.764; and SOL vs. SP, HR= 0.60, p = 0.054). Median OS was 15.4/21.6/12.6 months (SL vs. SP, HR = 0.83, p = 0.443; and SOL vs. SP, HR = 0.51, p = 0.011) after median follow-up of 18.8 months. Incidences (%) of grade 3/4 toxicities were neutropenia 6/26/35, anemia 8/15/24, lymphopenia 2/6/10, leucopenia 4/6/12, anorexia 13/28/20, diarrhea 4/17/0, stomatitis 4/13/0. Updated OS data 18 months after enrollment of the last patient will be presented at this meeting.

Conclusions

In this randomized phase II study, SL showed a similar RR to SP, and SOL demonstrated promising efficacies with tolerable toxicities, suggesting the superiority to SP. A phase III trial of SOL versus SP is warranted.

Disclosure

K. Yamaguchi: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb I have honoraria to disclose. Name of entity:Taiho Pharmaceutical Co., LTD., Bristol Myers Squibb; S. Hironaka: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha I have honoraria to disclose. Name of entity:Taiho Pharmaceutical Co., LTD., Yakult Honsha; N. Sugimoto: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha I have honoraria to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha; T. Moriwaki: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD. I have honoraria to disclose. Name of entity:Taiho Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; Y. Komatsu: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; T. Nishina: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; A. Tsuji: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD. I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; T.E. Nakajima: I have an advisory relationship and research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD. I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb;M. Gotoh: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Bristol Myers Squibb I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD; N. Machida: I have research funding and honoraria to disclose. Name of entity:Tahio Pharmaceutical Co., LTD; N. Fuse: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD; T. Esaki: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; Y. Emi: I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; Y. Takinishi: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; S. Matsumoto: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; N. Boku: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha; H. Baba: I have research funding to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb I have honoraria to disclose. Name of entity: Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb; I. Hyodo: I have an advisory relationship to disclose. Name of entity:Yakult Honsha I have research funding and honoraria to disclose. Name of entity:Tahio Pharmaceutical Co., LTD., Yakult Honsha, Bristol Myers Squibb.