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Multicenter phase II study of SOX plus trastuzumab for patients with HER2+ metastatic or recurrent gastric cancer: KSCC/HGCSG/CCOG/PerSeUS 1501B

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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.

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Acknowledgements

We sincerely thank the participating patients and their families. We are indebted to the physicians and all other medical staff. We also thank Ms. Sakamoto and the staff at the CReS Kyushu for their excellent data collection and management, secretarial assistance, and support. We thank Marla Brunker, from Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript. This work was supported by the CReS Kyushu with funding from Yakult Honsha Co., Ltd., (KSCC1501B) Japan, under a research contract.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan

    Satoshi Yuki

  2. Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan

    Katsunori Shinozaki

  3. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Tomomi Kashiwada

  4. Department of Gastroenterological Surgery/Clinical Research Institute Cancer Research Division, National Kyushu Medical Center, Fukuoka, Japan

    Tetsuya Kusumoto

  5. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Masaaki Iwatsuki & Hideo Baba

  6. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan

    Hironaga Satake

  7. Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Kazuma Kobayashi

  8. Department of Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Taito Esaki

  9. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Yuichiro Nakashima, Eiji Oki & Masaki Mori

  10. Department of Gastroenterological Surgery, Clinical Research Institute, National Hospital Organization Beppu Medical Center, Beppu, Japan

    Hirofumi Kawanaka

  11. Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan

    Yasunori Emi

  12. Division of Cancer Center, Hokkaido University Hospital, Sapporo, Japan

    Yoshito Komatsu

  13. Yamaguchi University, Ube, Japan

    Mototsugu Shimokawa

  14. Department of Hematology/Oncology, Japan Community Health Care Organization, Kyushu Hospital, Kitakyushu, Japan

    Akitaka Makiyama

  15. Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan

    Hiroshi Saeki

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  1. Satoshi Yuki
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  17. Hideo Baba
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  18. Masaki Mori
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Corresponding author

Correspondence to Eiji Oki.

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Conflict of interest

This study was supported by funding from Yakult Honsha Co., Ltd. S. Yuki has received honoraria for lecturing, from Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan, K.K., Takeda Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Bristol-Meyers Squibb Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Taiho Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., and Merck Serono Co., Ltd. E. Oki has received honoraria for lecturing, from Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Johnson & Johnson K.K., Merck Serono Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Yakult Honsha Co., Ltd. All remaining authors have declared no conflicts of interest.

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Yuki, S., Shinozaki, K., Kashiwada, T. et al. Multicenter phase II study of SOX plus trastuzumab for patients with HER2+ metastatic or recurrent gastric cancer: KSCC/HGCSG/CCOG/PerSeUS 1501B. Cancer Chemother Pharmacol 85, 217–223 (2020). https://doi.org/10.1007/s00280-019-03991-3

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  • DOI: https://doi.org/10.1007/s00280-019-03991-3

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