Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer: Results of single arm phase IV COMACHI study

Abstract

Background: CLEOPATRA study demonstrated the efficacy and safety of pertuzumab (P) + trastuzumab (T) + docetaxel (D) but efficacy results of Japanese subgroup weren't consistent with the whole study results. A phase IV, multicenter, prospective, COMACHI study was conducted in Japan to re-confirm the efficacy and safety of P+T+D demonstrated in the CLEOPATRA study. Methods: Patients (pts) with HER2-positive breast cancer who were diagnosed as Stage IV or recurred more than a year after (neo)adjuvant taxane chemotherapy completion were enrolled. Pts were administered study drugs intravenously every 3 weeks. Discontinuation of D was allowed after cycle 6. After discontinuation of D, pts were given maintenance by T+P, however not allowed to receive hormonal therapy for HR positive pts. We defined PFS as the primary endpoint. To demonstrate a median PFS of 12.4 months (mos) or more, which was observed in the placebo arm in the CLEOPATRA study. Results: From November 2013 to September 2015, 132 pts were enrolled and all pts were treated with T+P at least once. The median age was 56.5 years old and 102 pts (77.3%) had not received prior HER2 therapy. Median cycles of T and P were both 24.0 (range 2.0-71.0) and that of D was 6.0 (range 0.0-65.0). Pts characteristics and subgroup analysis results are shown in the Table below. [Table presented] Median PFS was 22.8 mos [95% CI, 16.9-34.8], and thereby a median PFS of 12.4 mos or more was confirmed. The incidence of typical Grade 3/4 adverse events were febrile neutropenia (31.1%), neutropenia (24.2%), leukopenia (10.6%), and diarrhea (4.5%), and these findings are consistent with the CLEOPATRA study except for febrile neutropenia. Febrile neutropenia lead to only one case of treatment discontinuation and it was manageable. Conclusions: The efficacy and safety of P+T+D in Japanese pts were consistent with those of the CLEOPATRA study and we confirmed this treatment as a standard care at 1st line therapy for HER2-positive metastatic breast cancer. Legal entity responsible for the study: Chugai Pharmaceutical Co., Ltd. Funding: Chugai Pharmaceutical Co., Ltd. Disclosure: N. Masuda: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Kyowa-Kirin; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Officer / Board of Directors: Japan Breast Cancer Research Group Association. S. Ohtani: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: AstraZeneca. S. Nagai: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli-Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd. Y. Komoike: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli-Lilly; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, the publisher, for writing atricle: Nikkei Business Publications, Inc. Y. Ito: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self): Eisai; Research grant / Funding (institution): Covance; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): A2healthcare; Research grant / Funding (institution): Parexel; Research grant / Funding (institution): Kyowa-Kirin. M. Ikeda: Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Asahi Kasei Pharma Corporation; Speaker Bureau / Expert testimony: Kyowa-Kirin; Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: Mundipharma; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Nippon Kayaku; Research grant / Funding (institution): Hisamitsu; Officer / Board of Directors, engaged in the project of medical practice guidline: Japanese Breast cancer society; Officer / Board of Directors, the leader of clinical trial comittee: Setouchi Breast Project Comprehensive Support Organization. K. Ishida: Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Nippon Kayaku. T. Nakayama: Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli-Lilly; Speaker Bureau / Expert testimony: Novartis. T. Takashima: Speaker Bureau / Expert testimony, Officer / Board of Directors: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Officer / Board of Directors: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Kyowa-Kirin; Speaker Bureau / Expert testimony: Eli-Lilly. T. Asakawa: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. S. Matsumoto: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. D. Shimizu: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. M. Takahashi: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Eli-Lilly; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Kyowa-Kirin; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Daiichi Sankyo; Speaker Bureau / Expert testimony: Allergan; Speaker Bureau / Expert testimony, Research grant / Funding (institution): FUJIFILM Toyama Chemical; Speaker Bureau / Expert testimony: Nihon Medi-Physics; Honoraria (self), for wrtitin article: The Asahi Shimbun Company. All other authors have declared no conflicts of interest.