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Effectiveness of eribulin as first-line or second-line chemotherapy for HER2-negative hormone-resistant advanced or metastatic breast cancer: findings from the multi-institutional, prospective, observational KBCRN A001: E-SPEC study

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Abstract

Background

The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting.

Methods

This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model.

Results

Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07–2.68) and 1.75 (95% CI, 1.28–2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (n = 98) was 2.56 years (95% CI 2.27–2.74), while it was 2.87 years (95% CI 2.20–4.32) for those who avoided anthracycline and taxane as first- and second-line (n = 48) (adjusted HR, 1.20; 95% CI 0.70–2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14–2.75) and 2.91 years (95% CI 2.61–4.32) for those aged < 65 and ≥ 65 years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56–1.46).

Conclusions

Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting.

Trial registration

This study is registered with Clinical Trials.gov (NCT 02,551,263).

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Acknowledgements

The Translational Research Center for Medical Innovation (TRI) conducted this study jointly with the Kobe City Medical Center General Hospital, Kyoto University Hospital, and other medical institutions. We would like to thank Dr. Tabuchi, Ms. Nomura, Ms. Nakagawa, Mr. Kidena, and the investigators of the KBCRN E-SPEC study as well as the patients who participated in the study. We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by Eisai Co., Ltd. Eisai was not involved in the design and conduct of the study or in the data analysis and interpretation of the results. A quadripartite contract for conducting this study was made between Eisai, Kobe City Medical Center General Hospital, Kyoto University and TRI.

Author information

Authors and Affiliations

  1. Department of Breast Surgery, Kansai Medical University, Hirakata-city, Osaka, 573-1191, Japan

    Yuichiro Kikawa & Tomoharu Sugie

  2. Department of Breast Surgery, Kobe City Medical Center General Hospital, Kobe-city, Hyogo, 650-0047, Japan

    Yuichiro Kikawa

  3. Department of Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto-city, Kyoto, 606-8507, Japan

    Takeshi Kotake, Masahiro Takada & Masakazu Toi

  4. Department of Breast Surgery, Kansai Electric Power Hospital, Osaka-city, Osaka, 553-0003, Japan

    Takeshi Kotake & Nobuko Ogura

  5. Department of Breast Surgery, Osaka Red Cross Hospital, Osaka-city, Osaka, 543-8555, Japan

    Shigeru Tsuyuki & Yookija Kang

  6. Department of Breast Surgery, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka-city, Osaka, 530-8480, Japan

    Sachiko Takahara & Yuri Fujimoto

  7. Department of Breast Surgery, Tenri Hospital, Tenri-city, Nara, 632-0018, Japan

    Hiroyasu Yamashiro

  8. Wakayama Breast Clinic, Wakayama-city, Wakayama, 640-8203, Japan

    Hiroshi Yoshibayashi

  9. Department of Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, Kyoto-city, Kyoto, 602-8566, Japan

    Rie Yasuoka, Katsuhiko Nakatsukasa & Tetsuya Taguchi

  10. Department of Breast Surgery, Shinko Hospital, Kobe-city, Hyogo, 651-0072, Japan

    Kazuhiko Yamagami

  11. Department of Breast Surgery, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki-city, Hyogo, 660-8550, Japan

    Hirofumi Suwa

  12. Department of Breast Surgery, Kobe City Nishi-Kobe Medical Center, Kobe-city, Hyogo, 651-2273, Japan

    Toshitaka Okuno

  13. Department of Breast Surgery, Kyoto Min-Iren Chuo Hospital, Kyoto-city, 616-8147, Japan

    Ichiro Nakayama

  14. Department of Breast Surgery, Yamato Takada Municipal Hospital, Yamatotakada-city, Nara, 635-8501, Japan

    Tatsushi Kato

  15. Department of Breast Surgery, Kyoto City Hospital, Kyoto-city, Kyoto, 604-8845, Japan

    Yoshio Moriguchi

  16. Breast Oncology Service, Saitama Medical University International Medical Center, Hidaka-city, Saitama, 350-1298, Japan

    Hiroshi Ishiguro

  17. Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe-city, Hyogo, 650-0047, Japan

    Tatsuo Kagimura

Authors
  1. Yuichiro Kikawa
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  2. Takeshi Kotake
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  3. Shigeru Tsuyuki
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  5. Sachiko Takahara
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  6. Yuri Fujimoto
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  9. Masahiro Takada
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  11. Katsuhiko Nakatsukasa
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  20. Tatsuo Kagimura
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Corresponding author

Correspondence to Yuichiro Kikawa.

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Conflict of interest

Yuichiro Kikawa received honoraria from Eisai, Novartis, Pfizer, Eli Lilly, Taiho, and Chugai, outside the submitted work. Hiroyasu Yamashiro received honoraria from Chugai, Daiich-Sankyo, Pfizer, Kyowa Kirin, Eisai, Eli Lilly, Takeda, and Taiho, outside the submitted work. Masahiro Takada received honoraria from Chugai, AstraZeneca, Pfizer, Eli Lilly, Eisai, Daiichi Sankyo, and Kyowa-Kirin as well as grants from Eisai and Nipponkayaku, outside the submitted work. Hiroshi Ishiguro received honoraria from JMS, Taiho, Daiichi-Sankyo, Eisai, Chugai, and Kyowa-Hakko-Kirin outside the submitted work and is on the board of directors of the JBCRG association, Kyoto Breast cancer Research Network; he is also an Executive Committee member of Japan Supportive, Palliative and Psychosocial Oncology Group. Tatsuo Kagimura received grants from Eisai, during the conduct of the study. Tetsuya Taguchi received honoraria from Eisai, Daiichi Sankyo, and Chugai, outside the submitted work. Tomoharu Sugie received honoraria from Chugai, Eisai, Pfizer, Astra Zeneca, Lilly, MSD, Novaris, Takeda, Kyowa-Kirin, Genomic Health, and Devicor as well as grants from KBBM, outside the submitted work. Masakazu Toi received grants and honoraria from Chugai, Takeda, Pfizer, Kyowa-Hakko-Kirin, Taiho, Eisai, Daiichi-Sankyo, Astra Zeneca, Shimadzu, and Nippon Kayaku; honoraria from Eli Lilly, MSD, Genomic Health, Novartis, Konica Minolta, BMS, and Yakult; grants from JBCRG association, Astellas, and AFI technologies, outside the submitted work; and is on the board of directors of the JBCRG association, Organisation for Oncology and Translational Research, and Kyoto Breast cancer Research Network. The remaining authors have no conflicts of interest to disclose.

Ethics approval

The institutional review board at each study site approved the final protocol. This study was conducted in accordance with the Japanese Guidelines for Clinical Research of the Ministry of Health, Labour and Welfare and the Declaration of Helsinki.

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All participants provided written informed consent prior to study participation.

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Kikawa, Y., Kotake, T., Tsuyuki, S. et al. Effectiveness of eribulin as first-line or second-line chemotherapy for HER2-negative hormone-resistant advanced or metastatic breast cancer: findings from the multi-institutional, prospective, observational KBCRN A001: E-SPEC study. Breast Cancer 29, 796–807 (2022). https://doi.org/10.1007/s12282-022-01357-x

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