Anthracycline-containing regimens or taxane versus S-1 as first-line chemotherapy for metastatic breast cancer

• Published in: British journal of cancer Vol. 125; no. 9; pp. 1217 - 1225
• Main Authors: Mukai, Hirofumi, Uemura, Yukari, Akabane, Hiromitsu, Watanabe, Takanori, Park, Youngjin, Takahashi, Masato, Sagara, Yoshiaki, Nishimura, Reiki, Takashima, Tsutomu, Fujisawa, Tomomi, Hozumi, Yasuo, Kawahara, Takuya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-10-2021; Nature Publishing Group
• Subjects: 631/67/1059; 631/67/1347; Adult; Aged; Anthracycline; Anthracyclines - administration & dosage; Anthracyclines - pharmacology; Antineoplastic Agents, Hormonal - therapeutic use; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cancer Research; Cancer therapies; Chemotherapy; Drug Combinations; Drug Resistance; Drug Resistance, Neoplasm - drug effects; Endocrine therapy; Epidemiology; ErbB-2 protein; Female; Humans; Metastases; Metastasis; Middle Aged; Molecular Medicine; Neoplasm Metastasis; Oncology; Oxonic Acid - administration & dosage; Oxonic Acid - pharmacology; Patients; Receptor, ErbB-2 - genetics; Survival; Survival Analysis; Taxanes; Taxoids - administration & dosage; Taxoids - pharmacology; Tegafur - administration & dosage; Tegafur - pharmacology; Treatment Outcome; Young Adult
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-021-01531-6

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.