Abstract P1-03-01: Eribulin versus S-1 as first- or second- line chemotherapy to assess Health-related Quality of Life and overall survival in HER2-negative metastatic breast cancer (RESQ study): a non-inferiority, randomized controlled trial
Authors: Kikawa Yuichiro , Kashiwabara Kosuke , Taira Naruto , Iwatani Tsuguo , Shimozuma Kojiro , Ohtani Shoichiro , Yoshinami Tetsuhiro , Watanabe Junichiro , Kashiwaba Masahiro , Watanabe Ken-ichi , Kitada Masahiro , Sakaguchi Koichi , Tanabe Yuko , Aihara Tomohiko , Mukai Hirofumi , Takahashi Masato 
Published: March 2023

Abstract
Background Eribulin is a chemotherapeutic drug that prolongs overall survival (OS) in patients with HER2-negative metastatic breast cancer (MBC), mainly in third-line or later chemotherapy (ChT) [1]. However, health-related quality of life (HRQOL) and efficacy in patients who receive eribulin as first- or second-line therapy is not well known. In contrast, S-1, an oral 5-fluorouracil derivative, shows similar OS to taxanes as first-line ChT and better HRQOL, based on a large phase III trial conducted in Japan [2]. Here, we compared the effect on HRQOL and efficacy of eribulin and S-1 in MBC patients in a first- or second-line ChT setting. Methods We planned an open-label, multicenter, randomized controlled phase III study at 50 hospitals in Japan. We enrolled patients with HER2-negative MBC who had no or one previous ChT for MBC regardless of prior administration of anthracyclines and taxanes. Patients were randomly assigned (1:1) to either eribulin (1.4 mg/m² administered on days 1 and 8 of a 21-day) or S-1 (40–60 mg twice daily for 14 consecutive days, followed by a 7-day break). Randomization was stratified by institution, age, treatment line, hormone receptor status, and time from surgery to recurrence. HRQOL assessment was conducted using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 questions (QLQ-C30) every six weeks until week 24, and then every nine weeks until week 42 after baseline assessment. The primary outcome measure was the global health status (GHS) score of EORTC QLQ-C30, with a prespecified non-inferiority margin of 10% for a difference in the proportion of patients experiencing deterioration at one year. Clinically meaningful deterioration was defined as a ≥ 10-point decrease from baseline GHS score or death. Secondary outcomes were OS, progression-free survival (PFS), and adverse events. We estimated that the study needed 330 patients to obtain 80% power for non-inferiority. This trial was registered with the University Hospital Medical Information Network, Japan (protocol ID 000021398). Results Between June 2016 and October 2019, 302 patients were enrolled, with 152 assigned to eribulin and 148 to S-1. The full analysis set for HRQOL assessment included 134 and 136 patients, while that for efficacy consisted of 141 and 144 patients, respectively. Overall compliance with the questionnaire was 85.6 %. Among the full analysis set for efficacy, 28 (19.9%) and 31 (21.5%) cases were triple negative, respectively. Eribulin and S-1 were administered as first-line ChT in 99 (70.2%) and 101 (70.1%) patients, respectively. Risk difference of GHS deterioration through one year for the eribulin versus S1 group was -0.66% (95% CI -12.47 to 11.16; P non-inferiority =0.077). Median time to first deterioration in GHS score was 5.64 months (95% CI 3.51–8.00) and 5.28 months (95% CI 3.28-7.80) (HR 1.07 [95% CI 0.79–1.45]; P =0.667); median OS was 35.0 months (95% CI 27.2-41.0) and 27.8 months (95% CI 24.6-33.5) (HR 0.69 [95% CI 0.50-0.95]; P=0.023); and median PFS was 6.07 months (95% CI 5.48-7.80) and 6.66 months (95% CI 5.48-7.77), respectively (HR 0.90 [95% CI 0.68-1.18]; P=0.427). No previously unrecognized adverse events were observed. Conclusions We found a marginal non-inferiority in HRQOL for eribulin, albeit that the difference was not statistically significant owing to the smaller than planned sample size. Time to first clinically meaningful deterioration was almost identical between the two arms, whereas OS was significantly extended with eribulin. These findings indicate that eribulin in first- or second-line ChT is acceptable as a standard regimen in this patient population. [1] Lancet 2011; 377: 914–23 [2] Lancet Oncol 2016; 17: 90–98
Citation Format: Yuichiro Kikawa, Kosuke Kashiwabara, Naruto Taira, Tsuguo Iwatani, Kojiro Shimozuma, Shoichiro Ohtani, Tetsuhiro Yoshinami, Junichiro Watanabe, Masahiro Kashiwaba, Ken-ichi Watanabe, Masahiro Kitada, Koichi Sakaguchi, Yuko Tanabe, Tomohiko Aihara, Hirofumi Mukai, Masato Takahashi. Eribulin versus S-1 as first- or second- line chemotherapy to assess Health-related Quality of Life and overall survival in HER2-negative metastatic breast cancer (RESQ study): a non-inferiority, randomized controlled trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-03-01.