title: Meta-analysis supporting noninferiority of oxaliplatin plus S-1 to cisplatin plus S-1 in first-line treatment of advanced gastric cancer (G-SOX study): indirect comparison with S-1 alone.
abstract: BACKGROUND
  The Randomized Phase III Study Comparing Oxaliplatin plus S-1 with Cisplatin plus S-1 in Chemotherapy-naïve Patients with Advanced Gastric Cancer (G-SOX) showed the noninferiority of S-1 (an oral fluoropyrimidine-derivative dihydropyrimidine dehydrogenase inhibitor) plus oxaliplatin combination therapy (SOX) to S-1 plus cisplatin therapy (CS) in overall survival [hazard ratio (HR) from proportional hazard model 0.958, 95 % confidence interval (CI) 0.803-1.142; noninferiority margin 1.15]. To further clarify the clinical position of SOX in advanced gastric cancer (AGC), a meta-analysis including information from other reported studies was conducted.
  
  
  METHODS
  In addition to G-SOX, Japanese phase III clinical trials including S-1 monotherapy were included in the analyses. Individual patient data for SOX (318 patients) and CS (324 patients) from G-SOX, as well as those for S-1 (160 patients) from the Randomized Phase III Study Comparing the Efficacy and Safety of Irinotecan plus S-1 with S-1 Alone as First-line Treatment for Advanced Gastric Cancer (GC0301/TOP-002), were available. Published clinical information for S-1 from other studies (total 705 patients) was also collected. A Weibull distribution was assumed for overall survival time, and parameters for SOX, CS, and S-1 were estimated parametrically. Posterior HR distributions were obtained with a Bayesian approach.
  
  
  RESULTS
  The HR of SOX to S-1 was 0.817 (95 % credible interval 0.704-0.939), and the probability of the HR <1.00 was 99.8 %. The HR of CS to S-1 was 0.871 (95 % credible interval; 0.754-0.998), and the probability of the HR <1.00 was 97.6 %. The HR of SOX to CS in G-SOX was 0.942 (95 % credible interval; 0.789-1.117), and the probability of HR <1.15 was 98.9 %.
  
  
  CONCLUSIONS
  This meta-analysis indicates that SOX was superior to S-1 and noninferior to CS in AGC.
authors.affiliation: Faculty of Engineering, Tokyo University of Science, 1-3, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan. hamada@ms.kagu.tus.ac.jp.
authors.forename: Chikuma
authors.initials: C
authors.lastname: Hamada
authors.affiliation: Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, 2-1-1, Asamizodai, Minami-ku, Sagamihara, 252-0380, Japan.
authors.forename: Mizutomo
authors.initials: M
authors.lastname: Azuma
authors.affiliation: Department of Surgery, Osaka General Medical Center, 3-1-56, Bandaihigashi, Sumiyoshi-ku, Osaka, 558-0056, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Cancer Chemotherapy Center, Osaka Medical College Hospital, 2-7, Daigakumachi, Takatsuki, 569-8686, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Division of Gastrointestinal Oncology and Digestive Endoscopy, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-0882, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bando
authors.affiliation: Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160, Minamiumemotomachi, Matsuyama, 791-0280, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.affiliation: Department of Gastroenterology, Ibaraki Prefectural Central Hospital, 6528, Koibuchi, Kasama, 309-1703, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Amagai
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of JFCR, 3-8-31, Ariake, Tokyo, 135-8550, Japan.
authors.forename: Keisho
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authors.lastname: Chin
authors.affiliation: Department of Endoscopy, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Niwa
authors.affiliation: Department of Medical Oncology, Kochi Health Sciences Center, 2125-1, Ike, Kochi, 781-8555, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Department of Surgery, Sakai City Hospital, 1-1-1, Minamiyasui-cho, Sakai, 590-0064, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imamura
authors.affiliation: Department of Gastroenterological Oncology, Hyogo Cancer Center, 13-70, Kitaoji-cho, Akashi, 673-0021, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007, Nagaizumi-cho, Shimonagakubo, Sunto-gun, 411-8777, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Division of Clinical Oncology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, 329-0498, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Division of Gastroenterology, Saitama Cancer Center, 780, Inamachi, Oaza Komuro, Kita-adachi-gun, 362-0806, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Medical Oncology, National Hospital Organization Kyoto Medical Center, 1-1, Fukakusamukaihata-cho, Fushimi-ku, Kyoto, 612-0861, Japan.
authors.forename: Hisateru
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Clinical Trial Promotion Department, Chiba Cancer Center, 666-2, Nitona-cho, Chuo-ku, Chiba, 260-0801, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hironaka
authors.affiliation: Department of Internal Medicine, Showa University Northern Yokohama Hospital, Chigasakichuo, Tsuzuki-ku, Yokohama, 224-0032, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, 663-8131, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
authors.affiliation: Division of Gastroenterology, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, 305-8577, Japan.
authors.forename: Ichinosuke
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authors.lastname: Hyodo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D004338:Drug Combinations; D006801:Humans; D000077146:Irinotecan; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy*; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin
keywords: Bayesian; Gastric cancer; Indirect comparison; Meta-analysis; Noninferiority; Oxaliplatin