Hirofumi Mukai1, Yukari Uemura2, Hiromitsu Akabane3, Takanori Watanabe4, Youngjin Park5, Masato Takahashi6, Yoshiaki Sagara7, Reiki Nishimura8, Tsutomu Takashima9, Tomomi Fujisawa10, Yasuo Hozumi11, Takuya Kawahara12. 1. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Chiba, Japan. hrmukai@east.ncc.go.jp. 2. Biostatistics Section, Department of Data Science, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan. 3. Department of Surgery, Asahikawa-Kosei General Hospital, Asahikawa, Hokkaido, Japan. 4. Department of Breast Cancer, National Hospital Organization Sendai Medical Center, Sendai, Japan. 5. Department of Breast and Endocrine Surgery, Tohoku Medical and Pharmaceutical University, Miyagi, Japan. 6. Department of Breast Surgery, National Organization Hokkaido Cancer Center, Sapporo, Hokkaido, Japan. 7. Department of Breast Center, Hakuaikai Medical Corp Sagara Hospital, Kagoshima, Japan. 8. Department of Breast Oncology, Kumamoto Shinto General Hospital, Kumamoto City, Kumamoto, Japan. 9. Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 10. Department of Breast Oncology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan. 11. Department of Breast and Endocrine Surgery, University of Tsukuba Hospital/ Ibaraki Prefectural Central Hospital, Kasama City, Ibaraki, Japan. 12. Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan.
Abstract
BACKGROUND: We have previously demonstrated S-1 is non-inferior to taxane with respect to overall survival as first-line chemotherapy for HER2-negative metastatic breast cancer. We aimed to confirm whether S-1 is also non-inferior to anthracycline-containing regimens in the same setting. METHODS: We conducted an open-label, non-inferiority, Phase 3 study. Individuals who had HER2-negative metastatic breast cancer, had received no chemotherapy for advanced disease and had endocrine therapy resistance, were randomly assigned to the anthracycline-containing regimens or S-1. The primary endpoint was overall survival. A pre-planned combined analysis of our two Phase 3 studies was also carried out. RESULTS: We enrolled 230 patients (anthracycline, n = 115; S-1, n = 115). Median overall survival was 30.1 months (95% CI 24.9-35.8) with the S-1 group and 33.7 months (95% CI 25.5-36.9) with the anthracycline group. The HR for the anthracycline group was 1.09 (95% CI 0.80-1.48). The combined analysis constituted 814 patients (395 assigned to standard treatment (anthracycline or taxane); 419 assigned to S-1). Median overall survival was 36.3 months in the standard treatment group and 32.7 months in the S-1 group. S-1 was non-inferior to standard treatment in terms of overall survival (HR 1.06 (95% CI 0.90-1.25); P non-inferiority = 0.0062). CONCLUSIONS: S-1 could be considered a new treatment option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer. CLINICAL TRIAL REGISTRATION: The University Hospital Medical Information Network, Japan: UMIN000005449. This trial was registered on 15 April, 2011.
BACKGROUND: We have previously demonstrated S-1 is non-inferior to taxane with respect to overall survival as first-line chemotherapy for HER2-negative metastatic breast cancer. We aimed to confirm whether S-1 is also non-inferior to anthracycline-containing regimens in the same setting. METHODS: We conducted an open-label, non-inferiority, Phase 3 study. Individuals who had HER2-negative metastatic breast cancer, had received no chemotherapy for advanced disease and had endocrine therapy resistance, were randomly assigned to the anthracycline-containing regimens or S-1. The primary endpoint was overall survival. A pre-planned combined analysis of our two Phase 3 studies was also carried out. RESULTS: We enrolled 230 patients (anthracycline, n = 115; S-1, n = 115). Median overall survival was 30.1 months (95% CI 24.9-35.8) with the S-1 group and 33.7 months (95% CI 25.5-36.9) with the anthracycline group. The HR for the anthracycline group was 1.09 (95% CI 0.80-1.48). The combined analysis constituted 814 patients (395 assigned to standard treatment (anthracycline or taxane); 419 assigned to S-1). Median overall survival was 36.3 months in the standard treatment group and 32.7 months in the S-1 group. S-1 was non-inferior to standard treatment in terms of overall survival (HR 1.06 (95% CI 0.90-1.25); P non-inferiority = 0.0062). CONCLUSIONS: S-1 could be considered a new treatment option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer. CLINICAL TRIAL REGISTRATION: The University Hospital Medical Information Network, Japan: UMIN000005449. This trial was registered on 15 April, 2011.
Authors: T Shirasaka; K Nakano; T Takechi; H Satake; J Uchida; A Fujioka; H Saito; H Okabe; K Oyama; S Takeda; N Unemi; M Fukushima Journal: Cancer Res Date: 1996-06-01 Impact factor: 12.701