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Long-term survival analysis of addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer

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Abstract

Purpose

Addition of carboplatin (CBDCA) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) has improved pathological complete response (pCR) rates in previous studies. We present long-term survival outcomes (disease-free survival [DFS], pre-planned secondary endpoint; overall survival [OS], post hoc exploratory endpoint) of our randomized study of the addition of CBDCA to NAC for HER2-negative breast cancer.

Methods

Patients with stage II/III, HER2-negative breast cancer (N = 179) were randomly assigned to receive CP–CEF (four 3-week cycles of CBDCA [area under the curve, 5 mg/mL/min, day 1] and weekly paclitaxel [wPTX, 80 mg/m2, day 1, 8, 15] followed by four 3-week cycles of cyclophosphamide, epirubicin, and 5-fluorouracil [CEF, 500/100/500 mg/m2]) or P–CEF (four cycles of wPTX followed by four cycles of CEF) as NAC. DFS and OS were analyzed at each population of pCR status and assigned treatment arm.

Results

Of 179 patients, 154 were available for long-term follow-up. At a median follow-up of 6.6 years (range, 0.7–8.0 years), patients who achieved pCR [n = 42, 23.5% (CP–CEF: n = 28, P–CEF: n = 16)] had longer DFS and OS than non-pCR patients [DFS; HR 0.15 (0.04–0.61), P = 0.008, OS; log-rank P = 0.003]. Addition of carboplatin to NAC significantly improved DFS and OS in the subset of patients with TNBC [DFS: HR, 0.22 (0.06–0.82), P = 0.015; OS: HR, 0.12 (0.01–0.96), P = 0.046], but not in the subset of patients with hormone receptor-positive disease or among all patients.

Conclusions

Addition of carboplatin to neoadjuvant chemotherapy significantly improved DFS and OS in patients with TNBC but not in those with hormone receptor-positive, HER2-negative breast cancer.

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Funding

This study was supported by the Health and Labour Sciences Research Grants (Clinical Cancer Research), Ministry of Health, Labour and Welfare (Grant Number: MHLW, 2009 Clinical Cancer Research General-020) and the Cancer Research and Development grants, and National Cancer Center (Grant Number: 2011-A-42).

Author information

Authors and Affiliations

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

    Madoka Iwase & Hiroji Iwata

  2. Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan

    Madoka Iwase

  3. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    Madoka Iwase

  4. Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Masashi Ando

  5. Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan

    Kenjiro Aogi

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

    Tomoyuki Aruga

  7. Division of Breast Oncology, Saitama Cancer Center, Saitama, Japan

    Kenichiro Inoue

  8. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan

    Akihiko Shimomura

  9. Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Eriko Tokunaga

  10. Division of Breast, Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Norikazu Masuda

  11. Department of Breast Surgical Oncology, St. Luke’s International Hospital, Tokyo, Japan

    Hideko Yamauchi

  12. Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan

    Toshinari Yamashita

Authors
  1. Madoka Iwase
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  2. Masashi Ando
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  4. Tomoyuki Aruga
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  7. Eriko Tokunaga
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  8. Norikazu Masuda
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  9. Hideko Yamauchi
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  11. Hiroji Iwata
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Corresponding author

Correspondence to Masashi Ando.

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Conflict of interest

MA has declared the conflicts related to personal fees from Astra Zeneca K. K., Novartis Pharma K. K., Chugai Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K. K., and Taiho pharmaceutical CO., LTD.; KA received personal fees as honoraria from Chugai Pharmaceutical, Eisai, AstraZeneca, Taiho Pharmaceutical, Novartis Pharma, Daiichi Sankyo, Mochida Pharmaceutical, Ono Pharmaceutical, and Eli Lilly Japan, and his institution received research funds from Chugai Pharmaceutical, Eisai and Sanofi.; TA reports personal fees from CHUGAI PHARMACEUTICAL CO., LTD and Pfizer Japan Inc during the conduct of the study.; KI reports personal fees from Eisai, Chugai, Pfizer, and Eli Lilly, and reports grants from Novartis, Pfizer, Chugai, Daiichi Sankyo, Parexel/Puma Biotechnology, MSD, Bayer, Eli Lilly, and Eisai.; AH reports personal fees from Chugai Pharmaceutical, AstraZeneca, Pfizer, Eli Lilly, Eisai, Daiichi Sankyo, and Novartis, outside the submitted work.; NM has received honoraria from Chugai, AstraZeneca, Pfizer, Eli Lilly, Eisai, and Takeda; funding from Chugai, AstraZeneca, Kyowa Hakko Kirin, MSD, Novartis, Pfizer, Eli Lilly, Eisai, and Daiichi Sankyo.; HY reports personal fees from AstraZeneca K.K., TAIHO PHARMACEUTICAL CO., LTD., Allergan Japan K.K., Pfizer Japan Inc., CHUGAI PHARMACEUTICAL CO., LTD., Novartis Pharma K.K., Shionogi & Co., Ltd., Takeda Pharmaceutical Co., Ltd., NIPPONKAYAKU CO., LTD., TOWA PHARMACEUTICAL CO., LTD., and Elsevier Japan KK during the conduct of the study.; TY reports personal fees as honoraria from Chugai, Eisai, Novartis, Taiho, Nippon Kayaku, AstraZeneca, Kyowa Kirin, Pfizer Japan, and Eli Lilly; and reports grants from Chugai, Taiho, Nippon Kayaku, and Kyowa kirin, outside the submitted work.; HI reports grants and personal fees from Chugai, personal fees from AstraZeneca, personal fees from Daiichi Sankyo, grants and personal fees from Novartis, grants from MSD, grants and personal fees from Lilly, personal fees from Kyowa Hakko Kirin, personal fees from Pfizer, during the conduct of the study; All other authors have declared no conflicts of interest.

Ethical approval

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.

Informed consent

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

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Electronic supplementary material

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10549_2020_5580_MOESM1_ESM.png

Supplementary Fig.1: Comparison of the long-term survival of the intention-to-treat population according to pathological complete response (pCR) status.

10549_2020_5580_MOESM2_ESM.png

Supplementary Fig.2: Sensitivity analyses for hormone receptor-negative patients considering the use of additional adjuvant chemotherapy. Patients who received additional chemotherapy (n=19) were censored when the adjuvant treatment started.

10549_2020_5580_MOESM3_ESM.png

Supplementary Fig.3: The results of comparing prognosis between patients who completed and discontinued neoadjuvant chemotherapy. A Overall survival among all patients, B Disease-free survival among all patients, C Overall survival among HR-positive patients (n = 104), D Disease-free survival among HR-positive patients, E Overall survival among HR-negative patients (n = 75), F Disease-free survival in HR-negative patients.

Supplementary file4 (Supplementary Table 1) (XLSX 11 kb)

Supplementary file5 (Supplementary Table 2) (XLSX 13 kb)

Supplementary file6 (Supplementary Table 3) (XLSX 11 kb)

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Iwase, M., Ando, M., Aogi, K. et al. Long-term survival analysis of addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer. Breast Cancer Res Treat 180, 687–694 (2020). https://doi.org/10.1007/s10549-020-05580-y

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