Trastuzumab emtansine plus pertuzumab in Japanese patients with HER2-positive metastatic breast cancer: a phase Ib study
To investigate the safety, pharmacokinetics, and efficacy of trastuzumab emtansine (T-DM1) in combination with pertuzumab in Japanese patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.
Patients and methods
Patients with HER2-positive advanced or recurrent breast cancer who had received trastuzumab and chemotherapy-containing therapies were eligible. Patients received T-DM1 (3.6 mg/kg) with full-dose pertuzumab (a loading dose of 840 mg and then 420 mg) intravenously every 3 weeks. This study was registered at the Japan Pharmaceutical Information Center-Clinical Trials Information (JapicCTI-101234).
Six patients enrolled in this study. The median duration of treatment was 11 (range 1–32) cycles. The most common treatment-emergent adverse event (TEAE) for any grade was diarrhea. Grade 3 or greater TEAEs included aspartate aminotransferase increased, left ventricular ejection fraction (LVEF) decreased, and neutrophil count decreased. The dose-limiting toxicity of grade 3 LVEF decreased was observed in one patient during cycle 1; however, it resolved within 30 days. The pharmacokinetic parameters of T-DM1 and pertuzumab were not affected by co-administration of the drugs. The best overall response included a partial response (PR) in 3 patients (50%) and stable disease (SD) in 2 patients (33%).
The combination of T-DM1 and pertuzumab was tolerated and showed exploratory efficacy in Japanese patients with HER2-positive metastatic breast cancer.
KeywordsT-DM1 Trastuzumab emtansine Pertuzumab HER2-positive Metastatic breast cancer
We would like to thank the patients who participated in this trial and their families, the investigators, and all staffs who supported this trial.
This study was sponsored by Chugai Pharmaceutical Co., Ltd. and F. Hoffmann-La Roche Ltd.
Compliance with ethical standards
Conflict of interest
KT and JH declare no conflicts of interest. EN has received honoraria from Chugai and Novartis. MH has received honoraria from Chugai, AstraZeneca, Eli Lilly, Pfizer, Eisai, Daiichi-Sankyo, and Novartis. NS has received remuneration from Chugai, AstraZeneca, Eisai, Pfizer, and Taiho. KK and KM are employees of Chugai. HI has received grants from Chugai, AstraZeneca, Bayer, Eli Lilly, GSK, Kyowa Hakko Kirin, MSD, Novartis, and Pfizer; honoraria from Chugai, AstraZeneca, Eisai, and Pfizer. YF has received grants from Chugai and Takeda; honoraria from Chugai, Astra Zeneca, Daiichi-Sankyo, Eisai, Eli Lilly, Novartis, and Taiho.
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