Satoshi Yuki1, Katsunori Shinozaki2, Tomomi Kashiwada3, Tetsuya Kusumoto4, Masaaki Iwatsuki5, Hironaga Satake6, Kazuma Kobayashi7, Taito Esaki8, Yuichiro Nakashima9, Hirofumi Kawanaka10, Yasunori Emi11, Yoshito Komatsu12, Mototsugu Shimokawa13, Akitaka Makiyama14, Hiroshi Saeki15, Eiji Oki16, Hideo Baba5, Masaki Mori9. 1. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan. 2. Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan. 3. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan. 4. Department of Gastroenterological Surgery/Clinical Research Institute Cancer Research Division, National Kyushu Medical Center, Fukuoka, Japan. 5. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 6. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan. 7. Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 8. Department of Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 9. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 10. Department of Gastroenterological Surgery, Clinical Research Institute, National Hospital Organization Beppu Medical Center, Beppu, Japan. 11. Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan. 12. Division of Cancer Center, Hokkaido University Hospital, Sapporo, Japan. 13. Yamaguchi University, Ube, Japan. 14. Department of Hematology/Oncology, Japan Community Health Care Organization, Kyushu Hospital, Kitakyushu, Japan. 15. Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan. 16. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. okieiji@surg2.med.kyushu-u.ac.jp.
Abstract
BACKGROUND: Trastuzumab (T-mab) combined with cisplatin and fluoropyrimidines is a standard first-line treatment for HER2+ advanced gastric cancer (AGC). We conducted the first phase II trial among four Japanese study groups to assess the efficacy and safety of T-mab + S-1 and oxaliplatin (T-SOX130) for HER2+ AGC or recurrent gastric cancer. METHODS: Patients with IHC 3+ or IHC 2+/FISH+ tumors received 80 mg/m2 (80-120 mg/day) oral S-1 on days 1-14, 130 mg/m2 intravenous oxaliplatin on day 1, and intravenous T-mab (8 mg/kg loading dose, 6 mg/kg thereafter) on day 1 of a 21-day cycle. The primary endpoint was centrally assessed response rate (RR). Adverse events were based on the Common Terminology Criteria for Adverse Events (CTCAE) Ver.4.0. RESULTS: We enrolled 42 patients from June 2015 to May 2016. Efficacy and safety analyses were conducted for 39 patients. The data cutoff was May 31, 2018. The confirmed RR was 82.1% (32/39; 90% CI 70.0-90.0); the disease control rate was 87.2% (34/39; 95% CI 73.3-94.4). Nine patients underwent curative surgery after T-SOX130. Median Time to treatment failure (TTF), Progression-free survival (PFS) and Overall survival (OS) was 5.7 (95% CI 4.6-7.0), 7.0 (95% CI 5.5-14.1), and 27.6 (95% CI 15.6-Not reached) months, respectively. Incidences of grade 3-4 adverse events > 10% were thrombocytopenia (17.9%), anorexia (17.9%), anemia (12.8%), neutropenia (10.3%), and hyponatremia (10.3%). CONCLUSIONS: T-SOX130 showed promising response and survival with a favorable safety profile and should be considered for patients with HER2+ AGC.
BACKGROUND:Trastuzumab (T-mab) combined with cisplatin and fluoropyrimidines is a standard first-line treatment for HER2+ advanced gastric cancer (AGC). We conducted the first phase II trial among four Japanese study groups to assess the efficacy and safety of T-mab + S-1 and oxaliplatin (T-SOX130) for HER2+ AGC or recurrent gastric cancer. METHODS:Patients with IHC 3+ or IHC 2+/FISH+ tumors received 80 mg/m2 (80-120 mg/day) oral S-1 on days 1-14, 130 mg/m2 intravenous oxaliplatin on day 1, and intravenous T-mab (8 mg/kg loading dose, 6 mg/kg thereafter) on day 1 of a 21-day cycle. The primary endpoint was centrally assessed response rate (RR). Adverse events were based on the Common Terminology Criteria for Adverse Events (CTCAE) Ver.4.0. RESULTS: We enrolled 42 patients from June 2015 to May 2016. Efficacy and safety analyses were conducted for 39 patients. The data cutoff was May 31, 2018. The confirmed RR was 82.1% (32/39; 90% CI 70.0-90.0); the disease control rate was 87.2% (34/39; 95% CI 73.3-94.4). Nine patients underwent curative surgery after T-SOX130. Median Time to treatment failure (TTF), Progression-free survival (PFS) and Overall survival (OS) was 5.7 (95% CI 4.6-7.0), 7.0 (95% CI 5.5-14.1), and 27.6 (95% CI 15.6-Not reached) months, respectively. Incidences of grade 3-4 adverse events > 10% were thrombocytopenia (17.9%), anorexia (17.9%), anemia (12.8%), neutropenia (10.3%), and hyponatremia (10.3%). CONCLUSIONS: T-SOX130 showed promising response and survival with a favorable safety profile and should be considered for patients with HER2+ AGC.
Entities:
Keywords:
HER2-positive advanced gastric cancer; SOX plus trastuzumab
Authors: Sang Soo Eom; Wonyoung Choi; Bang Wool Eom; Sin Hye Park; Soo Jin Kim; Young Il Kim; Hong Man Yoon; Jong Yeul Lee; Chan Gyoo Kim; Hark Kyun Kim; Myeong-Cherl Kook; Il Ju Choi; Young-Woo Kim; Young Iee Park; Keun Won Ryu Journal: J Gastric Cancer Date: 2022-03-31 Impact factor: 3.720