Daisuke Takahari1, Keisho Chin2, Naoki Ishizuka3, Atsuo Takashima4, Keiko Minashi5, Shigenori Kadowaki6, Tomohiro Nishina7, Takako Eguchi Nakajima8, Kenji Amagai9, Nozomu Machida10, Masahiro Goto11, Keisei Taku12, Takeru Wakatsuki2, Hirokazu Shoji4, Shuichi Hironaka5,13, Narikazu Boku4, Kensei Yamaguchi2. 1. Department of Gastroenterology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. daisuke.takahari@jfcr.or.jp. 2. Department of Gastroenterology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. 3. Department of Clinical Trial Planning and Management, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 4. Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 5. Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan. 6. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 7. Department of Gastrointestinal Medical Oncology, Shikoku Cancer Center, Matsuyama, Japan. 8. Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan. 9. Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Kasama, Japan. 10. Department of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 11. Department of Cancer Chemotherapy Center, Osaka Medical College, Takatsuki, Japan. 12. Department of Medical Oncology, Shizuoka General Hospital, Shizuoka, Japan. 13. Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, Oita, Japan.
Abstract
BACKGROUND: Trastuzumab with cisplatin and fluoropyrimidines improves overall survival (OS) in patients with HER2-positive advanced gastric cancer (AGC). S-1 plus oxaliplatin (SOX) is one of the standard regimens for HER2-negative AGC in Japan. However, few studies have evaluated trastuzumab combined with SOX in patients with HER2-positive AGC. METHODS: This was a multicenter, phase II study conducted at 10 institutions in Japan. Patients with HER2-positive AGC received S-1 twice a day on days 1-14 and oxaliplatin and trastuzumab on day 1 of a 21-day cycle. The primary endpoint was the confirmed overall response rate (ORR), and the secondary endpoints were OS, progression-free survival (PFS), and safety. The sample size was 75 to have 90% power with an alpha error of 0.1 (one-sided), expecting an ORR of 65% and threshold of 50%. RESULTS: From June 2015 to January 2018, 75 patients were enrolled. The ORR was 70.7% [95% confidence interval (CI) 59.0-80.6]. The median OS and PFS were estimated as 18.1 months (95% CI 15.6-26.5) and 8.8 months (95% CI 7.4-12.2), respectively. The major grade 3 or 4 adverse events were sensory neuropathy (16.0%) and neutropenia (10.7%). CONCLUSIONS: Trastuzumab with SOX had promising activity with well-tolerated toxicities for patients with HER2-positive AGC. CLINICAL TRIAL REGISTRATION: UMIN000017602.
BACKGROUND:Trastuzumab with cisplatin and fluoropyrimidines improves overall survival (OS) in patients with HER2-positive advanced gastric cancer (AGC). S-1 plus oxaliplatin (SOX) is one of the standard regimens for HER2-negative AGC in Japan. However, few studies have evaluated trastuzumab combined with SOX in patients with HER2-positive AGC. METHODS: This was a multicenter, phase II study conducted at 10 institutions in Japan. Patients with HER2-positive AGC received S-1 twice a day on days 1-14 and oxaliplatin and trastuzumab on day 1 of a 21-day cycle. The primary endpoint was the confirmed overall response rate (ORR), and the secondary endpoints were OS, progression-free survival (PFS), and safety. The sample size was 75 to have 90% power with an alpha error of 0.1 (one-sided), expecting an ORR of 65% and threshold of 50%. RESULTS: From June 2015 to January 2018, 75 patients were enrolled. The ORR was 70.7% [95% confidence interval (CI) 59.0-80.6]. The median OS and PFS were estimated as 18.1 months (95% CI 15.6-26.5) and 8.8 months (95% CI 7.4-12.2), respectively. The major grade 3 or 4 adverse events were sensory neuropathy (16.0%) and neutropenia (10.7%). CONCLUSIONS:Trastuzumab with SOX had promising activity with well-tolerated toxicities for patients with HER2-positive AGC. CLINICAL TRIAL REGISTRATION: UMIN000017602.
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