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Clinical Studies

Anthracycline-containing regimens or taxane versus S-1 as first-line chemotherapy for metastatic breast cancer

British Journal of Cancer volume 125, pages 1217–1225 (2021)Cite this article

Subjects

Abstract

Background

We have previously demonstrated S-1 is non-inferior to taxane with respect to overall survival as first-line chemotherapy for HER2-negative metastatic breast cancer. We aimed to confirm whether S-1 is also non-inferior to anthracycline-containing regimens in the same setting.

Methods

We conducted an open-label, non-inferiority, Phase 3 study. Individuals who had HER2-negative metastatic breast cancer, had received no chemotherapy for advanced disease and had endocrine therapy resistance, were randomly assigned to the anthracycline-containing regimens or S-1. The primary endpoint was overall survival. A pre-planned combined analysis of our two Phase 3 studies was also carried out.

Results

We enrolled 230 patients (anthracycline, n = 115; S-1, n = 115). Median overall survival was 30.1 months (95% CI 24.9–35.8) with the S-1 group and 33.7 months (95% CI 25.5–36.9) with the anthracycline group. The HR for the anthracycline group was 1.09 (95% CI 0.80–1.48). The combined analysis constituted 814 patients (395 assigned to standard treatment (anthracycline or taxane); 419 assigned to S-1). Median overall survival was 36.3 months in the standard treatment group and 32.7 months in the S-1 group. S-1 was non-inferior to standard treatment in terms of overall survival (HR 1.06 (95% CI 0.90–1.25); P non-inferiority = 0.0062).

Conclusions

S-1 could be considered a new treatment option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer.

Clinical trial registration

The University Hospital Medical Information Network, Japan: UMIN000005449. This trial was registered on 15 April, 2011.

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Fig. 1
Fig. 2: Kaplan–Meier curves.
Fig. 3: A forest-plot analysis of overall survival.
Fig. 4: Change from baseline of health-related quality of life (global health status).

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Data availability

All datasets used and analysed during this study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all the patients, their families and the investigators who participated in this study.

Funding

This study was sponsored by the Comprehensive Support Project for Oncology Research (CSPOR) of the Public Health Research Foundation. The research fund was provided to CSPOR by Taiho Pharmaceutical Company Limited under the study contract. Taiho Pharmaceutical took no part in this study other than providing information relevant to the proper use of the study drug.

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Authors and Affiliations

  1. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Chiba, Japan

    Hirofumi Mukai

  2. Biostatistics Section, Department of Data Science, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan

    Yukari Uemura

  3. Department of Surgery, Asahikawa-Kosei General Hospital, Asahikawa, Hokkaido, Japan

    Hiromitsu Akabane

  4. Department of Breast Cancer, National Hospital Organization Sendai Medical Center, Sendai, Japan

    Takanori Watanabe

  5. Department of Breast and Endocrine Surgery, Tohoku Medical and Pharmaceutical University, Miyagi, Japan

    Youngjin Park

  6. Department of Breast Surgery, National Organization Hokkaido Cancer Center, Sapporo, Hokkaido, Japan

    Masato Takahashi

  7. Department of Breast Center, Hakuaikai Medical Corp Sagara Hospital, Kagoshima, Japan

    Yoshiaki Sagara

  8. Department of Breast Oncology, Kumamoto Shinto General Hospital, Kumamoto City, Kumamoto, Japan

    Reiki Nishimura

  9. Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan

    Tsutomu Takashima

  10. Department of Breast Oncology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan

    Tomomi Fujisawa

  11. Department of Breast and Endocrine Surgery, University of Tsukuba Hospital/ Ibaraki Prefectural Central Hospital, Kasama City, Ibaraki, Japan

    Yasuo Hozumi

  12. Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan

    Takuya Kawahara

Authors
  1. Hirofumi Mukai
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Contributions

HM contributed to the design of the study. HM, YU, TW, YS, RN, TT and YH were members of the executive committee that oversaw the conduct of the study. HM, HA, TW, YP, MT, YS, RN, TT, TF and YH contributed substantially to patient recruitment. HM and YU contributed to data collection. HM contributed to data review. YU and TK contributed to data analysis. All authors contributed to data interpretation. HM contributed to the writing of the report. All authors contributed to review of the report and approved the final submitted version.

Corresponding author

Correspondence to Hirofumi Mukai.

Ethics declarations

Ethics approval and consent to participate

The studies were done in accordance with the Ethical Guidelines for Clinical Research of the Japanese Ministry of Health, Labor and Welfare, and the Declaration of Helsinki. All participants gave written informed consent. An independent ethics committee for each participating site approved the protocol and any modifications. A full list of the ethical committees can be found in the Supplementary Information.

Consent to publish

Not applicable.

Competing interests

HM has received personal fees from Daiichi Sankyo, Taiho, and Takeda; funding from the Japanese government, Pfizer, and Daiichi Sankyo, outside the submitted work. MT has received personal fees from Taiho, Eisai, Pfizer, Astra Zeneca, Kyowa Kirin, Nippon Kayaku and Eli Lilly. TT has received personal fees from Taiho, Chugai Kyowa Hakko Kirin, Eisai, Pfizer, Novartis, Astra Zeneca and Takeda, outside the submitted work. The remaining authors declare no competing interests.

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Mukai, H., Uemura, Y., Akabane, H. et al. Anthracycline-containing regimens or taxane versus S-1 as first-line chemotherapy for metastatic breast cancer. Br J Cancer 125, 1217–1225 (2021). https://doi.org/10.1038/s41416-021-01531-6

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