S-1 as an option for second-line treatment of NSCLC. Is the ‘East Side Story’ applicable in the West?

S-1 is an oral fluoropyrimidine formulation that consists of tegafur (FT), gimeracil, and oteracil in a molar ratio of 1 : 0.4 : 1 [1, 2]. FT is a prodrug of 5-fluorouracil (5-FU), gimeracil serves to maintain the plasma concentration of 5-FU by blocking its degradation, and oteracil limits gastrointestinal toxicity by inhibiting the activation of 5-FU in the gut (Figure 1). In this issue of Annals of Oncology, Nokihara et al. report the results of the EAST-LC trial, a phase III non-inferiority study comparing S-1 (80–120 mg/day, depending on body surface area, for days 1–28 of a 6-week cycle) with docetaxel in 1154 Asian patients with advanced non-small-cell lung cancer (NSCLC) previously treated with at least one platinum-based regimen [3]. The hazard ratio for overall survival (OS) was 0.945, with the upper limit of the 95% confidence interval (1.073) being smaller than the predefined margin of 1.2, thus demonstrating the non-inferiority of S-1. Furthermore, the EORTC QLQ-C30 score for global health status was higher in the S-1 arm. Whereas diarrhea, skin pigmentation, and stomatitis were more common in the patients treated with S-1, the frequency of febrile neutropenia, leukopenia, and alopecia was higher in the docetaxel arm.