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Comparison of S-1–cisplatin every 5 weeks with capecitabine-cisplatin every 3 weeks for HER2-negative gastric cancer (recurrent after S-1 adjuvant therapy or chemotherapy-naïve advanced): pooled analysis of HERBIS-2 (OGSG 1103) and HERBIS-4A (OGSG 1105) trials

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International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

We previously reported the HERBIS-4A phase II trial comparing S-1 plus cisplatin (SP) with capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2-negative advanced gastric cancer (GC). We performed a pooled analysis of HERBIS-4A and HERBIS-2, the phase II trial comparing SP with XP in HER2-negative recurrent GC patients with a recurrence-free interval after S-1 adjuvant therapy of ≥ 6 months.

Patients and methods

Patients were randomly assigned to receive either SP [S-1 (40–60 mg twice daily for 21 days) plus cisplatin (60 mg/m2 on day 8), every 5 weeks] or XP [capecitabine (1000 mg/m2 twice daily for 14 days) plus cisplatin (80 mg/m2 on day 1), every 3 weeks].

Results

In the pooled analysis, SP (n = 44–50) showed a longer progression-free survival [6.4 versus 5.1 months; hazard ratio (HR), 0.666; P = 0.062], overall survival (14.8 versus 10.6 months; HR, 0.695; P = 0.099), and time to treatment failure (4.6 versus 3.6 months; HR, 0.668; P = 0.045) as well as a higher disease control rate (86.4% versus 68.1%, P = 0.149) compared with XP (n = 47–51). A significant survival advantage for SP over XP was apparent in patients with a performance status of 0, a differentiated-type tumor histology, or a primary tumor localization to the upper portion of the stomach.

Conclusion

Our pooled analysis supports the use of SP in the first-line setting for patients with HER2-negative advanced or recurrent GC with a recurrence-free interval of ≥ 6 months.

Clinical trial registration

The HERBIS-2 trial was registered with UMIN-CTR as UMIN000006105.

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Acknowledgements

We thank all the patients, investigators, and medical staff at the participating institutions who contributed to this study.

Funding

This research was funded by Osaka Clinical Study Supporting Organization.

Author information

Author notes

  1. Hisato Kawakami and Kazumasa Fujitani contributed equally to this study.

Authors and Affiliations

  1. Department of Medical Oncology, Faculty of Medicine, Kindai University, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan

    Hisato Kawakami

  2. Department of Surgery, Osaka Prefectural General Medical Center, Osaka-shi, Japan

    Kazumasa Fujitani

  3. Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Japan

    Jin Matsuyama

  4. Department of Surgery, Ikeda Municipal Hospital, Ikeda, Japan

    Yusuke Akamaru

  5. Department of Surgery, Yao Municipal Hospital, Yao, Japan

    Shigeyuki Tamura

  6. Department of Surgery, Faculty of Medicine, Kindai University, Osaka-sayama, Japan

    Shunji Endo

  7. Department of Surgery, Sakai City Medical Center, Sakai, Japan

    Yutaka Kimura

  8. Department of Medical Oncology, Kindai University Nara Hospital, Ikoma, Japan

    Youichi Makari

  9. Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan

    Takao Tamura

  10. Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan

    Naotoshi Sugimoto & Taroh Satoh

  11. Cancer Center, Izumi City General Hospital, Izumi, Japan

    Daisuke Sakai

  12. Cancer Chemotherapy Center, Osaka Medical College Hospital, Takatsuki, Japan

    Toshimasa Tsujinaka

  13. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan

    Masahiro Goto & Toshio Shimokawa

  14. Clinical Study Support Center, Wakayama Medical University, Wakayama, Japan

    Yukinori Kurokawa

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  1. Hisato Kawakami
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for the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG)

Corresponding author

Correspondence to Hisato Kawakami.

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Conflict of interest

H.K. has received consulting fees from Bristol-Myers Squibb Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Daiichi-Sankyo Co. Ltd., and Taiho Pharmaceutical Co. Ltd; honoraria from Bristol-Myers Squibb Co. Ltd., AstraZeneca K.K., Bayer yakuhin Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Taiho Pharmaceutical Co. Ltd.; lecture fees from Bristol-Myers Squibb Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Taiho Pharmaceutical Co., Ltd.; and research funding from Chugai Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd, and Eisai Co. Ltd. T. Tamura has received honoraria from Merck Serono Co. Ltd., speaker’s bureau fees from Daiichi Sankyo Co. Ltd., and research funding from Takeda Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., and Taiho Pharmaceutical Co. Ltd. Y. Kurokawa has received lecture fees from Taiho Pharmaceutical Co. Ltd., Yakult Honsha, Ono Pharmaceutical Co. Ltd., MSD K.K., Daiichi Sankyo Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Kaken Pharmaceutical, as well as research grants from Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., and MSD K.K. T. Satoh received research grants from Giliad; consulting fees from Daiichi Sankyo and and Takeda Pharmaceutical, Co. Ltd.; consulting fees, honoraria and research grants from Merck BioPharm, Bristol-Myers K.K., Taiho pharmaceutical, Elli lilly, MSD,, Sanofi, Bristol Myers-Squib; and departmental research grants, research grants, honoraria and consulting fees from Chugai Pharmaceutical Co. Ltd., Ono Pharmaceutical. Co. Ltd. and Yakult Honsha Co. Ltd. All remaining authors declare no conflicts of interest.

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Kawakami, H., Fujitani, K., Matsuyama, J. et al. Comparison of S-1–cisplatin every 5 weeks with capecitabine-cisplatin every 3 weeks for HER2-negative gastric cancer (recurrent after S-1 adjuvant therapy or chemotherapy-naïve advanced): pooled analysis of HERBIS-2 (OGSG 1103) and HERBIS-4A (OGSG 1105) trials. Int J Clin Oncol 25, 1635–1643 (2020). https://doi.org/10.1007/s10147-020-01711-z

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