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Outcomes of fulvestrant therapy among japanese women with advanced breast cancer: a retrospective multicenter cohort study (JBCRG-C06; Safari)

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Abstract

Purpose

This retrospective study evaluated the effect of clinical background and treatment line on time to treatment failure (TTF) in advanced/metastatic breast cancer (AMBC) patients receiving F500 in Japan (UMIN 000015168).

Methods

Patients who commenced F500 treatment were registered at 16 sites in Japan. Correlations between baseline clinicopathological factors, treatment line, and TTF were investigated by Kaplan–Meier analysis. TTF data were analyzed using univariate analysis and multivariate analysis with a Cox proportional hazards model.

Results

Data for 1072 patients were available; 1031 patients (96.2%) were evaluable for efficacy. F500 was administered as first-line treatment in 2.0%, second-line in 22.7%, third-line in 26.7%, and ≥fourth-line in 48.6% patients. Median TTF was 5.4 months. Multivariate analysis found that earlier F500 use (first and second vs. third vs. ≥fourth line; hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.74–0.86; P < 0.001), longer period from AMBC diagnosis to F500 use (≥3 vs. <3 years; HR 0.60, 95% CI 0.51–0.70; P < 0.001), and no prior palliative chemotherapy administered for unresectable or metastatic breast cancer (no vs. yes; HR 0.69, 95% CI 0.60–0.80; P < 0.001) were associated with significantly longer TTF. Among 691 patients, where information on histologic/nuclear grade was available, a low grade was also associated with a longer TTF, but this finding was not maintained among patients with recurrent breast cancer (N = 558). Among women with recurrent breast cancer, a longer DFI between a patient’s initial breast cancer diagnosis and their recurrence was associated with a longer TTF on F500 therapy.

Conclusions

Our study showed that treatment period of F500 was longer when used in earlier-line treatment. For patients on F500, TTF was also longer for patients who had not received prior palliative chemotherapy and for those who had a longer period from their AMBC diagnosis to F500 use.

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Abbreviations

AE:

Adverse event

AI:

Aromatase inhibitor

AMBC:

Advanced/metastatic breast cancer

BC:

Breast cancer

CI:

Confidence interval

DFI:

Disease-free interval

ER:

Estrogen receptor

F250:

Fulvestrant 250 mg

F500:

Fulvestrant 500 mg

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

JBCRG:

The Japan Breast Cancer Research Group

OS:

Overall survival

PD:

Progressive disease

PgR:

Progesterone receptor

QOL:

Quality of life

SERD:

Selective estrogen receptor degrader

TAM:

Tamoxifen

TTF:

Time to treatment failure

TTP:

Time to progression

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Acknowledgements

We thank the patients who participated in this study. We also thank our colleagues who participated in this study and are not included in the list of authors, in alphabetical order: T. Takano (Toranomon Hospital), H. Yamashita (Hokkaido University Hospital), and D. Yotsumoto (Social medical corporation Hakuaikai, Sagara Hospital). We appreciate the contributions of data entry assistants from AC Medical INC. We also appreciate the contribution to management from the Japan Breast Cancer Research Group (JBCRG) administrative office and IBEC Co., Ltd. The authors would like to acknowledge H. Nikki March, PhD, and Mary Richardson, MSc, of Edanz Group for providing medical writing services.

Funding information

This work was supported by the Japan Breast Cancer Research Group (JBCRG) and AstraZeneca. Results from this study have previously been presented at EBCC10 on 11 May 2016.

Author information

Authors and Affiliations

  1. Department of Breast Surgery, Matsuyama Red Cross Hospital, 1 Bunkyo-cho, Matsuyama, Ehime, 790-8524, Japan

    H. Kawaguchi

  2. Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka, 540-0006, Japan

    N. Masuda

  3. Department of Breast and Endocrine Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, 537-0025, Japan

    T. Nakayama

  4. Department of Breast Oncology, Shikoku Cancer Center, Matsuyama, 791-0280, Japan

    K. Aogi

  5. Department of Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, 802-0077, Japan

    K. Anan

  6. Breast Medical Oncology Department, The Cancer Institute Hospital Of JFCR, Tokyo, 135-8550, Japan

    Y. Ito

  7. Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, 730-8518, Japan

    S. Ohtani

  8. Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, 951-8566, Japan

    N. Sato

  9. Department of Medical Oncology, Fukushima Medical University, Fukushima, 960-1295, Japan

    S. Saji

  10. Department of Breast Oncology, Kyushu Cancer Center, Fukuoka, 811-1395, Japan

    E. Tokunaga

  11. Department of Surgery, Division of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, 142-8666, Japan

    S. Nakamura

  12. Department of Breast Surgery, Hirosaki Municipal Hospital, Hirosaki, 036-8187, Japan

    Y. Hasegawa

  13. Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan

    M. Hattori

  14. Department of Breast Oncology, Gunma Prefectural Cancer Center, Ohta, 373-8550, Japan

    T. Fujisawa

  15. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan

    S. Morita

  16. Department of Breast Surgery, JCHO Kurume General Hospital, Kurume, 830-0013, Japan

    M. Yamaguchi

  17. Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 113-8677, Japan

    T. Yamashita

  18. Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 135-8550, Japan

    Y. Yamamoto

  19. Breast Oncology Center, The Cancer Institute Hospital Of JFCR, Tokyo, 135-8550, Japan

    S. Ohno

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

    M. Toi

Authors
  1. H. Kawaguchi
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  2. N. Masuda
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  3. T. Nakayama
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  4. K. Aogi
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  5. K. Anan
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  6. Y. Ito
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  7. S. Ohtani
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  8. N. Sato
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  9. S. Saji
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  10. E. Tokunaga
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  11. S. Nakamura
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  12. Y. Hasegawa
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  13. M. Hattori
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  14. T. Fujisawa
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  15. S. Morita
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  16. M. Yamaguchi
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  17. T. Yamashita
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  18. Y. Yamamoto
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  19. S. Ohno
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  20. M. Toi
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Corresponding author

Correspondence to H. Kawaguchi.

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Conflict of Interest

Hidetoshi Kawaguchi—Remuneration: Chugai, AstraZeneca, Eisai, Kyowa Kirin, Novartis, Taiho; Consultant/advisory role: AstraZeneca, Chugai. Norikazu Masuda—Remuneration: Chugai, AstraZeneca, Eisai, Kyowa Kirin. Takahiro Nakayama—Remuneration: Chugai, Novartis, AstraZeneca. Kenjiro Aogi—Remuneration: AstraZeneca. Keisei Anan—Remuneration: Chugai, AstraZeneca, Eisai, Novartis. Yoshinori Ito—Funding: Chugai, Novartis, Parexel, Eisai, Taiho, EPS, AstraZeneca, Sanofi, MSD, Daiichi Sankyo. Shigehira Saji—Remuneration: AstraZeneca; Funding: AstraZeneca. Satoshi Morita—Remuneration: AstraZeneca. All remaining authors have declared no conflicts of interest.

Ethical approval

The study was conducted in accordance with the Helsinki Declaration, ‘Guidelines for Clinical Evaluation Methods of Anti-Cancer Drugs’, and ‘Ethical Guidelines for Epidemiology Research (revised December 1, 2008)’.

Informed consent

This was an observational study that used only existing material, as defined in the “Ethical Guidelines for Epidemiology Research” co-published by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour, and Welfare of Japan. The purpose, details, and method of collection and usage of data are published on the JBCRG website relevant to each subject population. The Institutional Ethics Committee of each study site determined whether it was necessary to publish the study results. Thus, written informed consent was not necessary.

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Kawaguchi, H., Masuda, N., Nakayama, T. et al. Outcomes of fulvestrant therapy among japanese women with advanced breast cancer: a retrospective multicenter cohort study (JBCRG-C06; Safari). Breast Cancer Res Treat 163, 545–554 (2017). https://doi.org/10.1007/s10549-017-4212-x

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  • DOI: https://doi.org/10.1007/s10549-017-4212-x

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