Efficacy of the eribulin, pertuzumab, and trastuzumab combination therapy for human epidermal growth factor receptor 2–positive advanced or metastatic breast cancer: a multicenter, single arm, phase II study (JBCRG-M03 study)

Investigational New Drugs - Tập 39 - Trang 217-225 - 2020
Toshinari Yamashita1, Hidetoshi Kawaguchi2, Norikazu Masuda3, Masahiro Kitada4, Kazutaka Narui5, Masaya Hattori6, Tetsuhiro Yoshinami7, Nobuki Matsunami8, Kazuhiro Yanagihara9, Teru Kawasoe10, Takeshi Nagashima11, Hiroko Bando12, Hiroshi Yano13, Yoshie Hasegawa14, Rikiya Nakamura15, Masahiro Kashiwaba16, Satoshi Morita17, Shinji Ohno18, Masakazu Toi19
1Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan
2Department of Breast Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan
3Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka, Japan
4Breast Disease Center, Asahikawa Medical University Hospital, Asahikawa, Japan
5Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan
6Department of Breast Oncology, Aichi Cancer Center, Nagoya, Japan
7Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan
8Department of Breast Surgery, Osaka Rosai Hospital, Sakai, Japan
9Department of Medical Oncology, Kansai Electric Power Hospital, Osaka, Japan
10Department of Breast and Endocrine Surgery, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan
11Department of General Surgery, Chiba University Hospital, Chiba, Japan
12Breast and Endocrine Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
13Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
14Department of Breast Surgery, Hirosaki Municipal Hospital, Hirosaki, Japan
15Department of Breast Surgery, Chiba Cancer Center, Chiba, Japan
16Breast Surgery, Sagara Hospital, Kagoshima, Japan
17Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
18Center of Breast Oncology, The Cancer Institute Hospital of JFCR, Tokyo, Japan
19Department of Surgery (Breast Surgery), Graduate School of Medicine, Kyoto University, Kyoto, Japan

Tóm tắt

Purpose To date, it is not clear which anticancer agent is useful in combination with trastuzumab and pertuzumab As the first and second selective regimens for advanced or metastatic breast cancer (AMBC), this multicenter, open-label, phase II trial (JBCRG-M03: UMIN000012232) presents a prespecified analysis of eribulin in combination with pertuzumab and trastuzumab. Methods We enrolled 50 patients with no or single prior chemotherapy for HER2-positive AMBC during November 2013–April 2016. All patients received adjuvant or first-line chemotherapy with trastuzumab and a taxane. The treatment comprised eribulin on days 1 and 8 of a 21-day cycle and trastuzumabplus pertuzumab once every 3 weeks, all administered intravenously. While the primary endpoint was the progression-free survival (PFS), secondary endpoints were the response rate and safety. Results Of 50 patients, 49 were eligible for safety analysis, and the full analysis set (FAS) included 46 patients. We treated 8 (16%) and 41 (84%) patients in first- and second-line settings, respectively. While 11 patients (23.9%) had advanced disease, 35 (76.1%) had metastatic disease. The median PFS was 9.2 months for all patients [95% confidence interval (CI): 7.0–11.4]. In the FAS, 44 patients had the measurable lesions and the complete response rate (CR) was 17.4%, and partial response rate (PR) was 43.5%. The grade 3/4 adverse events were neutropenia (5 patients, 10.2%), including febrile neutropenia (2 patients, 4.1%), hypertension (3 patients, 6.1%), and other (1 patient). The average of the left ventricular ejection fraction did not decline markedly. No symptomatic left ventricular systolic dysfunction was observed. Conclusions In patients with HER2-positive AMBC, eribulin, pertuzumab, and trastuzumab combination therapy exhibited substantial antitumor activity with an acceptable safety profile. Hence, we have started a randomized phase III study comparing eribulin and a taxane in combination with pertuzumab and trastuzumab for the treatment of HER2-positive AMBC. Trial registration ID: UMIN-CTR: UMIN000012232.

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Investigational New Drugs

Tập 39

217-225

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