The postoperative adjuvant use of the oral fluoropyrimidine S-1 significantly reduced invasive disease-free survival (iDFS) events and improved 5-year iDFS estimates in primary breast cancer patients having hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease in combination with standard endocrine therapy, with a feasible safety profile.
Although long-term prognostic outcomes of primary breast cancer patients have been improved remarkably in recent years, recurrence of the disease remains a serious problem. In a Japanese study, the usefulness of S-1 in combination with adjuvant endocrine therapy for primary breast cancer patients with luminal disease was assessed . S-1 is a combination drug based on a biochemical modification of fluorouracil, containing tegafur, gimeracil, and oteracil in a molar ratio of 1:0.4:1. The study was designed as an open-label, randomised, phase 3 trial, and carried out in 139 centres in Japan. Stage I-III primary breast cancer patients aged 20-75 years with HR-positive, HER2-negative status and intermediate or higher risk of recurrence were randomly assigned (1:1) to receive standard endocrine therapy alone (control arm) or endocrine therapy plus S-1 (S-1 arm). S-1 was administered at a specified dose of 80, 100, or 120 mg/day, based on creatinine clearance (≥80 ml/min) and body surface area (BSA), for 1 year with a 2 weeks on/1 week off administration schedule. Baseline demographic characteristics were comparable between the 2 patient groups. Recurrence risk assessment was performed using anatomical stage, pathological findings such as histologic grade, and centrally confirmed proliferative marker status. The primary endpoint was iDFS, defined as time from randomisation to invasive disease recurrence, occurrence of second invasive cancer event, or death, and was analysed on an intention-to-treat (ITT) basis. Secondary endpoints included DFS, distant DFS, overall survival, and safety. A total of 1,959 patients were enrolled of which 1,932 patients were included in the full analysis set (control arm n=973; S-1 arm n=959).
The results of the pre-specified interim analysis met the primary endpoint, and this trial was terminated early at a median follow-up of 51.4 months. S-1 significantly reduced invasive events; 153 iDFS events were reported in the control arm and 99 iDFS events in the S-1 arm (HR 0.63; 95% CI 0.49-0.81; P=0.0003). The 5-year iDFS estimate was 81.6% in the control arm and 86.9% in the S-1 arm (155 iDFS events in the control arm and 101 in the S-1 arm). Distant recurrence as the first disease event was observed in 6.8% of patients in the S-1 arm and in 9.5% of those in the control arm. The safety data in patients treated with S-1 was consistent with the known profile of S-1 (see Table).
Table. Safety overview 
AEs, adverse events; ALT, alanine aminotransferase; AST, aspartate aminotransferase
1. Toi M, et al. GS1-09. SABCS 2019.
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Table of Contents: SABCS 2019
Screening, Detection, and Diagnosis
Phase 2 Trial Update
Phase 3 Trial Update
Long-Term Study Results
Triple-Negative Breast Cancer
HER2-Positive Breast Cancer
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