Systemic chemotherapy with anti-HER2 therapy is the standard of care for HER2-positive advanced breast cancer. Patient outcomes have improved remarkably with the use of novel anti-HER2 drugs, including trastuzumab (H), pertuzumab (P), and trastuzumab emtansine (T-DM1). The combination treatment comprising H, P, and docetaxel (D) (HPD) is highly recommended as the 1st-line treatment for patients with HER2-positive advanced breast cancer. In contrast, for elderly patients over 65 years of age, this regimen seems to be intolerable mentally and physically, and impairs their quality of life. A new standard treatment with less toxicity and non-inferior efficacy for elderly patients is needed.
We have planned a randomized, multicenter, open-label, phase III trial to confirm the non-inferiority of T-DM1 compared to HPD in terms of overall survival (OS) in elderly patients with HER2-positive advanced breast cancer. The eligibility criteria are as follows: 1) histologically proven HER2-positive breast cancer with metastatic disease 2) age 65-74 years with a performance status (PS) score 0-2, or 75-79 years with a PS score 0-1, and 3) no anti-HER2 therapy with chemotherapy for breast cancer, excluding peri-operative adjuvant therapy. Patients will be randomized to receive either HPD (H 6 mg/kg, P 420 mg/body, and D 60 mg/m2) or T-DM1 3.6 mg/kg every 3 weeks. The dose up of D (75 mg/m2) from the second cycle is defined based on the data regarding safety during the first cycle. The primary endpoint is OS. The secondary endpoints are progression-free survival, response rate, adverse events, breast cancer-related death, and deterioration of activities of daily living. The trial has been designed to achieve 70% power to confirm non-inferiority of T-DM1 compared with HPD at a one-sided alpha of 5% with a non-inferiority margin of 1.3 in terms of hazard ratio. With a median OS of 30 months in both arms, 6 years of accrual, and 5 years of follow up, 312 pts are required, and the planned sample size is 330. The study commenced in January 2018.Clinical trial information: UMIN000030783.
Clinical trial identification
Legal entity responsible for the study
Japan Agency for Medical Research and Development.
N. Niikura: Research fund: Chugai Pharmaceutical CO., Ltd. S. Saji: Honoraria for lecture: Eisai, Chugai and Pfizer; Research grant: Taiho and Chugai. N. Masuda: Honoraria: Chugai, AstraZeneca, Pfizer and Takeda; Research funding: Chugai, AstraZeneca, Kyowa-kirin, MSD, Novartis, Pfizer Eli-Lilly and Daiichi-Sankyo. F. Nagashima: Research funding: Taiho, Ono, Oncotherapy, Merck, Zeria, Lilly Japan, Takeda, Chugai, Yakult, Sumitomo Dainippon, Daiichi Sankyo, Shionogi, Novartis, J-Pharma, Bristol-Myers Squibb, Kyowa Hakko Kirin, Mochida, Astellas, Bayer, MSD, Eisai, Janssen. H. Iwata: Honoraria: Chugai, Daiichi Sankyo, AstraZeneca, Pfizer; Consultant: Chugai, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly, Novartis, AstraZeneca, Pfizer; Received research funding: Chugai, MSD, Kyowa Hkao Kirin, GSK, Daiichi Sankyo, Chugai, Lilly, Novartis, Bayer and Pfizer. All other authors have declared no conflicts of interest.