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Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial

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Abstract

Purpose

The randomized phase III JO21095 trial compared the efficacy and safety of low-dose capecitabine plus docetaxel combination therapy (XT) versus single-agent administration of docetaxel in anthracycline-pretreated HER2-negative metastatic breast cancer.

Methods

Patients were randomized to either low-dose XT (capecitabine 825 mg/m2 twice daily, days 1–14; docetaxel 60 mg/m2, day 1 every 3 weeks) or docetaxel (70 mg/m2, day 1 every 3 weeks). The primary objective was to demonstrate superior progression-free survival (PFS) with low-dose XT versus single-agent docetaxel. Overall survival (OS) and safety were secondary endpoints.

Results

In total, 162 patients were treated. Median PFS was 10.5 months with low-dose XT and 9.8 months with single-agent docetaxel (hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.40–0.97]; p = 0.03). The OS HR was 0.89 (95% CI 0.52–1.53; p = 0.68). Grade ≥3 treatment-related toxicities occurred in 74% of XT-treated patients and 76% of docetaxel-treated patients. The main differences in grade ≥3 treatment-related toxicities were hand-foot syndrome (7.3% of XT-treated patients vs 0% receiving docetaxel), fatigue/malaise (2.4 vs 10.0%), and peripheral edema (1.2 vs 7.5%). Dose modifications were required in 100% of low-dose XT and 49% of docetaxel patients. Toxicity-related treatment discontinuations occurred in 18 and 33%, respectively.

Conclusion

The improved PFS with low-dose XT versus docetaxel alone is consistent with higher-dose XT phase III experience, but the safety profile was more favorable and manageable.

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Acknowledgements

The authors wish to thank the patients and their families, study site personnel, and the study team for their participation in the trial. The JO21095 study was conducted by Chugai Pharmaceutical to fulfill a post-marketing commitment. Chugai Pharmaceutical was involved in the study design, statistical analyses, and data interpretation. Chugai Clinical Research Center Co., Ltd., gathered and managed data, and Quintiles Transnational Japan K. K. was responsible for data monitoring. The principal investigators (IH, NM, and KK) had full access to all study data and had final responsibility for the publication. Chugai funded third-party writing assistance for this manuscript and provided by Jennifer Kelly (Medi-Kelsey Ltd, UK).

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Authors and Affiliations

  1. Department of Surgery, Kansai Medical University Medical Center, 10-15 Fumizono cho, Moriguchi City, Osaka, 570-8507, Japan

    Daigo Yamamoto

  2. Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan

    Nobuaki Sato

  3. Department of Breast Surgery, Sagara Hospital, Kagoshima, Japan

    Yoshiaki Rai

  4. Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Yutaka Yamamoto

  5. Department of Breast Surgical Oncology, Juntendo University Hospital, Tokyo, Japan

    Mitsue Saito

  6. Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

    Hiroji Iwata

  7. Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Norikazu Masuda

  8. Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan

    Shoji Oura

  9. Department of Breast Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Junichiro Watanabe

  10. Biostatistics Center, Kurume University, Fukuoka, Japan

    Satoshi Hattori

  11. Medical Affairs, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan

    Yoshimasa Matsuura

  12. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan

    Katsumasa Kuroi

Authors
  1. Daigo Yamamoto
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  2. Nobuaki Sato
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  3. Yoshiaki Rai
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  4. Yutaka Yamamoto
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  5. Mitsue Saito
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  6. Hiroji Iwata
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  7. Norikazu Masuda
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  8. Shoji Oura
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  9. Junichiro Watanabe
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  10. Satoshi Hattori
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  11. Yoshimasa Matsuura
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  12. Katsumasa Kuroi
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Corresponding author

Correspondence to Daigo Yamamoto.

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Conflict of interest

Y Yamamoto has received honoraria from Chugai Pharmaceutical; J. Watanabe received remuneration for speaker engagements from Chugai Pharmaceutical and Eizai; N. Masuda has received honoraria from Chugai Pharmaceutical, Astra-Zeneca and Kyowa Hakko Kirin; H. Iwata has received honoraria from Chugai Pharmaceutical and has served as a consultant or advisory role for Chugai Pharmaceutical; M. Saito has received funding from Eizai; S. Hattori has served as a consultant or advisory role for Chugai Pharmaceutical; D. Yamamoto, N. Sato, Y. Rai, S. Oura, Y. Matsuura, and K. Kuroi declare that they have no conflict of interest.

Ethical approval

The study was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. The ethical committee approved the study protocol, and all patients provided written informed consent before undergoing any study-specific procedure. The trial complies with current Japanese laws.

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Yamamoto, D., Sato, N., Rai, Y. et al. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat 161, 473–482 (2017). https://doi.org/10.1007/s10549-016-4075-6

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  • DOI: https://doi.org/10.1007/s10549-016-4075-6

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