A risk-based subgroup analysis of the effect of adjuvant S-1 in estrogen receptor-positive, HER2-negative early breast cancer

Purpose The Phase III POTENT trial demonstrated the efficacy of adding S-1 to adjuvant endocrine therapy for estrogen receptor-positive, HER2-negative early breast cancer. We investigated the efficacy of S-1 across different recurrence risk subgroups. Methods This was a post-hoc exploratory analysis of the POTENT trial. Patients in the endocrine-therapy-only arm were divided into three groups based on composite risk values calculated from multiple prognostic factors. The effects of S-1 were estimated using the Cox model in each risk group. The treatment effects of S-1 in patients meeting the eligibility criteria of the monarchE trial were also estimated. Results A total of 1,897 patients were divided into three groups: group 1 (≤ lower quartile of the composite values) ( N = 677), group 2 (interquartile range) ( N = 767), and group 3 (> upper quartile) ( N = 453). The addition of S-1 to endocrine therapy resulted in 49% (HR: 0.51, 95% CI: 0.33–0.78) and 29% (HR: 0.71, 95% CI 0.49–1.02) reductions in invasive disease-free survival (iDFS) events in groups 2 and 3, respectively. We could not identify any benefit from the addition of S-1 in group 1. The addition of S-1 showed an improvement in iDFS in patients with one to three positive nodes meeting the monarchE cohort 1 criteria ( N = 290) (HR: 0.47, 95% CI: 0.29–0.74). Conclusions The benefit of adding adjuvant S-1 was particularly marked in group 2. Further investigations are warranted to explore the optimal usage of adjuvant S-1.