Though advanced and metastatic epidermal growth factor receptor 2 (HER2)-positive disease is not curable, a small proportion of patients with HER2-positive metastatic breast cancer remain in prolonged complete remission with anti-HER2 treatment. We hypothesized that some cases of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer may be curable by trastuzumab. In this large, multicenter retrospective study, we aimed to assess the long-term outcomes for patients with a durable response to trastuzumab.
We retrospectively evaluated the data of patients diagnosed with HER2-positive metastatic breast cancer who received trastuzumab for more than 2 years as the first-line treatment. Patients diagnosed between April 1, 2001 and December 31, 2014 at 19 institutions in Japan were included in the analysis.
A total of 108 patients were evaluated. Sixteen were met to exclusion criteria. The median follow-up length was 7.7 years. Disease progression occurred in 44/108 (40.7%) patients and 13/108 (12%) patients died. The median progression-free survival was 11.2 years, and as more than 80% of patients were alive 10 years after metastatic breast cancer diagnosis. Of the 108 patients, 57 achieved a clinical complete response. Trastuzumab therapy was interrupted for 27 (47.4%) of these patients (based on the doctor’s recommendation for 19 patients, owing to adverse events for 4 patients, owing to unknown reasons for 3 patients, and at the request of 1 patient). Disease progression occurred in 4 of the 27 patients after the interruption of trastuzumab treatment. The median duration of trastuzumab therapy for all 27 patients was 5.1 years (0.9-9.3 years).
In conclusion, we found that some patients showed no evidence of disease after the interruption of trastuzumab therapy. Discontinuation of maintenance trastuzumab in this patient population after a limited time should be explored cautiously while awaiting a global collaborative effort for a randomized trial.
Clinical trial identification
Legal entity responsible for the study
A. Shimomura: Research funds from AstraZeneca. J. Watanabe: Honoraria from AstraZeneca Japan, Chugai Pharmaceuticals, Eisai, Novartis Pharma Japan, Taiho pharmaceutical. Advisory board member of AstraZeneca Japan, Eisai. A. Matsui: Lecture Fee: Chugai, Daiichi Sankyo, Eisai, AstraZeneca, Kyowa Kirin Pharmaceutical. Research Funds: Chugai, Daiichi Sankyo, Eisai, Takeda Pharmaceutical, Taiho Pharmaceutical. T. Shien: Lecture fee from AstraZeneca, Novartis, Eizai, Chugai. K. Tamura: Research funds from AstraZeneca, Daiichi Sankyo, Pfizer, MSD. S. Saji: Honoraria from AstraZeneca, Chugai Pharmaceutical, Eisai, Novartis Pharma. Research funds from AstraZeneca and Chugai Pharmaceutical. N. Masuda: Research funds from Chugai and Eisai. Honorarium from Chugai and AstraZeneca. Y. Tokuda: Lecture fee: Pfizer, AstraZeneca, Novartis, Galderma, Kyowa Hakko Kirin. Manuscript fee: Kyowa Hakko Kirin, Daiichi Sankyo. Research funds: Taiho, Eisai, Nippon Kayaku, Chugai, Kyowa Hakko Kirin, Takeda, Novartis, CSPOR. Consulting fee: Meiji. All other authors have declared no conflicts of interest.