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The efficacy of sequential second-line endocrine therapies (ETs) in postmenopausal estrogen receptor-positive and HER2-negative metastatic breast cancer patients with lower sensitivity to initial ETs

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Abstract

Purpose

Second-line endocrine therapy (ET) for estrogen receptor (ER)-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC) is offered based on the response to first-line ET. However, no clinical trials have evaluated the efficacy and safety of secondary ETs in patients with poor responses to initial ET. This study evaluated the efficacy of second-line ET in ER-positive and HER2-negative postmenopausal MBC patients with low or very low sensitivity to initial ET.

Methods

This multicenter prospective observational cohort study evaluated the response of 49 patients to second-line ETs in postmenopausal MBC patients with low or very low sensitivity to initial ET. The primary endpoint was the clinical benefit rate (CBR) for 24 weeks.

Results

Of the 49 patients assessed, 40 (82%) received fulvestrant in the second line, 5 (10%) received selective estrogen receptor modulators, 3 (6%) received aromatase inhibitors (AIs) alone, and 1 received everolimus with a steroidal AI. The overall CBR was 44.9% [90% confidence interval (CI): 34.6–57.6, p = 0.009]; CBR demonstrated similar significance across the progesterone receptor-positive (n = 39, 51.3%, 90% CI: 39.6–65.2, p = 0.002), very low sensitivity (n = 17, 58.8%, 90% CI: 42.0–78.8, p = 0.003), and non-visceral metastases (n = 25, 48.0%, 90% CI: 34.1–65.9, p = 0.018) groups. The median progression-free survival was 7.1 months (95% CI: 5.6–10.6).

Conclusion

Second-line ET might be a viable treatment option for postmenopausal patients with MBC with low and very low sensitivity to initial ET. Future studies based on larger and independent cohorts are needed to validate these findings.

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Acknowledgements

This study was conducted as a research support project of the General Incorporated Association of Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC). We would like to thank Editage (www.editage.com) for English language editing.

Funding

This study was funded by AstraZeneca.

Author information

Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Takayuki Iwamoto, Tadahiko Shien & Naruto Taira

  2. Department of Breast Oncology, Gunma Prefectural Cancer Center, Gunma, Japan

    Tomomi Fujisawa

  3. Department of Medical Oncology, Gunma Prefectural Cancer Center, Gunma, Japan

    Kazuhiro Araki

  4. Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Kentaro Sakamaki

  5. Department of Breast and Thyroid Surgery, Chiba University Hospital, Chiba, Japan

    Takafumi Sangai

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

    Yuichiro Kikawa

  7. Department of Breast Surgery, Hyogo Cancer Center, Hyogo, Japan

    Shintaro Takao

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

    Reiki Nishimura

  9. Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center, Hokkaido, Japan

    Masato Takahashi

  10. Breast Center, Aihara Hospital, Osaka, Japan

    Tomohiko Aihara

  11. Division of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Hirofumi Mukai

Authors
  1. Takayuki Iwamoto
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  2. Tomomi Fujisawa
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  3. Tadahiko Shien
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  13. Naruto Taira
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Corresponding author

Correspondence to Takayuki Iwamoto.

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Conflict of interest

TI, TF, TShien, KA, KS, TSangai, ST, RN, TA, HM, and NT declare no conflict of interest. YK received an honorarium from Eizai, Chugai, Novartis, Taiho, Pfizer, and Eli Lilly. MT received an honorarium from AstraZeneca, Eli Lilly, Eizai, and Pfizer, and research funding from Eizai, Kyowa Hakko Kirin, Taiho, and Nippon kayaku.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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12282_2020_1095_MOESM1_ESM.tif

Supplementary file 1 Supplementary Fig. 1 Kaplan–Meier curves for time to chemotherapy. (A) All patients (N = 49). (B) Fulvestrant (n = 40), CI confidence interval (TIF 55 kb)

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Iwamoto, T., Fujisawa, T., Shien, T. et al. The efficacy of sequential second-line endocrine therapies (ETs) in postmenopausal estrogen receptor-positive and HER2-negative metastatic breast cancer patients with lower sensitivity to initial ETs. Breast Cancer 27, 973–981 (2020). https://doi.org/10.1007/s12282-020-01095-y

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