Norikazu Masuda1, Hiroko Bando2, Takashi Yamanaka3, Takayuki Kadoya4, Masato Takahashi5, Shigenori E Nagai6, Shoichiro Ohtani7, Tomoyuki Aruga8, Eiji Suzuki9, Yuichiro Kikawa10, Hiroyuki Yasojima11, Hiroi Kasai12, Hiroshi Ishiguro13, Hidetaka Kawabata14, Satoshi Morita15, Hironori Haga16, Tatsuki R Kataoka16, Ryuji Uozumi15, Shinji Ohno17, Masakazu Toi9. 1. Department of Surgery, Breast Oncology, NHO Osaka National Hospital, 2-1-14 Hoenzaka, Chuou-ku, Osaka, Japan. nmasuda@alpha.ocn.ne.jp. 2. Breast and Endocrine Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. 3. Breast and Endocrine Surgery, Kanagawa Cancer Center, Kanagawa, Japan. 4. Department of Breast Surgery, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan. 5. Department of Breast Surgery, NHO Hokkaido Cancer Center, Hokkaido, Japan. 6. Division of Breast Oncology, Saitama Cancer Center, Saitama, Japan. 7. Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan. 8. Breast Surgery Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 9. Breast Cancer Unit, Kyoto University Hospital, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 10. Department of Breast Surgery, Kobe City Medical Center General Hospital, Hyogo, Japan. 11. Department of Surgery, Breast Oncology, NHO Osaka National Hospital, 2-1-14 Hoenzaka, Chuou-ku, Osaka, Japan. 12. Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan. 13. Breast Oncology Service, Saitama Medical University International Medical Center, Saitama, Japan. 14. Department of Breast and Endocrine Surgery, Toranomon Hospital, Tokyo, Japan. 15. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 16. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. 17. Breast Oncology Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan.
Abstract
PURPOSE: To investigate clinical usefulness of eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. METHODS: Patients in group A (aged < 65 years with homologous recombination deficiency, HRD, score≥ 42, or those at any age with germline BRCA mutation, gBRCAm) were randomized to 4 cycles of paclitaxel plus carboplatin (group A1) or eribulin plus carboplatin (group A2), followed by 4 cycles of anthracycline. Patients in group B (aged < 65 years with HRD score < 42, or aged ≥ 65 years without gBRCAm) were randomized to 6 cycles of eribulin plus cyclophosphamide (group B1) or eribulin plus capecitabine (group B2); non-responders to the first 4 cycles of the eribulin-based therapy received anthracycline. Primary endpoint was pCR rate (ypT0-is, ypN0; centrally confirmed). Main secondary endpoint was safety. RESULTS: The full analysis set comprised 99 patients. The pCR rate was 65% (90% CI, 46%-81%) and 45% (27%-65%) in groups A1 and A2, respectively, and 19% (8%-35%) in both groups B1 and B2. No major difference was seen in secondary endpoints, but peripheral neuropathy incidence was 74% in group A1, whereas it was 32%, 22%, and 26% in groups A2, B1, and B2, respectively. CONCLUSIONS: In patients aged < 65 years with high HRD score orgBRCAm, weekly paclitaxel plus carboplatin and eribulin plus carboplatin followed by anthracycline resulted in a pCR rate of > 60% and > 40%, respectively, suggesting potential usefulness of patient stratification using HRD; pCR tended to be low in patients with HRD-negative tumors. Neurotoxicity was less frequent with the eribulin-based regimen. TRIAL REGISTRATION: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with unique trial number UMIN000023162. The Japan Breast Cancer Research Group trial number is JBCRG-22.
RCT Entities:
PURPOSE: To investigate clinical usefulness of eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. METHODS:Patients in group A (aged < 65 years with homologous recombination deficiency, HRD, score ≥ 42, or those at any age with germline BRCA mutation, gBRCAm) were randomized to 4 cycles of paclitaxel plus carboplatin (group A1) or eribulin plus carboplatin (group A2), followed by 4 cycles of anthracycline. Patients in group B (aged < 65 years with HRD score < 42, or aged ≥ 65 years without gBRCAm) were randomized to 6 cycles of eribulin plus cyclophosphamide (group B1) or eribulin plus capecitabine (group B2); non-responders to the first 4 cycles of the eribulin-based therapy received anthracycline. Primary endpoint was pCR rate (ypT0-is, ypN0; centrally confirmed). Main secondary endpoint was safety. RESULTS: The full analysis set comprised 99 patients. The pCR rate was 65% (90% CI, 46%-81%) and 45% (27%-65%) in groups A1 and A2, respectively, and 19% (8%-35%) in both groups B1 and B2. No major difference was seen in secondary endpoints, but peripheral neuropathy incidence was 74% in group A1, whereas it was 32%, 22%, and 26% in groups A2, B1, and B2, respectively. CONCLUSIONS: In patients aged < 65 years with high HRD score or gBRCAm, weekly paclitaxel plus carboplatin and eribulin plus carboplatin followed by anthracycline resulted in a pCR rate of > 60% and > 40%, respectively, suggesting potential usefulness of patient stratification using HRD; pCR tended to be low in patients with HRD-negative tumors. Neurotoxicity was less frequent with the eribulin-based regimen. TRIAL REGISTRATION: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with unique trial number UMIN000023162. The Japan Breast Cancer Research Group trial number is JBCRG-22.
Entities:
Keywords:
BRCA mutation status; Eribulin; Homologous recombination deficiency score; Neoadjuvant chemotherapy; Pathological complete response; Triple-negative breast cancer
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