Abstract P1-14-07: Randomized phase 3 study of anthracycline-containing regimens versus S-1 as first-line treatment for metastatic breast cancer (SELECT BC-CONFIRM)–A combined analysis of two randomized phase 3 studies (SELECT BC-CONFIRM and SELECT BC)–
Authors: Park Y , Akabane H , Watanabe T , Takahashi M , Sagara Y , Nishimura R , Tsurutani J , Takashima T , Fujisawa T , Hozumi Y , Uemura Y , Mukai H 
Published: May 2019

Background: Anthracycline-containing regimens and taxane have been standard as the first-line chemotherapy for metastatic breast cancer (MBC). We conducted SELECT BC (randomized phase 3 study of taxane versus S-1 as first-line treatment for MBC) for evaluating the efficacy of S-1 for patients with HER2-negative MBC from 2006 to 2010 in Japan. This study demonstrated non-inferiority of S-1 in overall survival (OS) (median OS was 37.2 months in taxes group and 35.0 months in S-1 group (HR 1.05, 95% CI 0.86–1.27, p=0.015)), and superiority in health-related quality of life (HRQOL) to taxanes. S-1 was also shown as less toxic than taxane (Lancet Oncol 2016; 17: 90-98). S-1 might provide clinical benefit as first-line treatment for patients with HER2-negative MBC. To confirm this suggestion, we have conducted further study (randomized phase 3 study of anthracycline-containing regimens versus S-1 as first-line treatment for HER2-negative MBC: SELECT BC-CONFIRM) from 2011 to present, and a combined analysis of two randomized studies (SELECT-BC CONFIRM and SELECT-BC).

Methods: In SELECT BC-CONFIRM, 230 patients receiving first-line treatment for MBC were randomly assigned to either anthracycline group (n=115) or S-1 group (n=115). Anthracycline group patients received anthracycline-containing regimens (AC, EC, FAC, FEC, q3w) at the discretion of the treating physician. S-1 group patients received S-1 40–60 mg twice daily based on the patient's body surface area for 28 days on, 14-day off. The primary endpoint was OS, and secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), adverse events, HRQOL, and cost-effectiveness. The results were combined with SELECT-BC, to confirm the hypothesis that S-1 treatment is not inferior to the standard therapy (taxanes / anthracycline) for HER2-negative MBC.

Results: A combined analysis of the two studies showed that HR was 1.06, 95%CI 0.90-1.253, and p=0.0071 between the standard therapy group and S-1 group. In addition, the Bayesian posterior probability for which HR would be less than 1.333 was about 99.6%.

Conclusions: A combined analysis of SELECT BC-CONFIRM and SELECT BC clearly demonstrated that OS with S-1 was not inferior to that with the standard therapy in patients receiving first-line treatment for HER2-negative MBC. S-1 could become a standard therapy for this patient population.

Citation Format: Park Y, Akabane H, Watanabe T, Takahashi M, Sagara Y, Nishimura R, Tsurutani J, Takashima T, Fujisawa T, Hozumi Y, Uemura Y, Mukai H. Randomized phase 3 study of anthracycline-containing regimens versus S-1 as first-line treatment for metastatic breast cancer (SELECT BC-CONFIRM)–A combined analysis of two randomized phase 3 studies (SELECT BC-CONFIRM and SELECT BC)– [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-14-07.