Background Concurrent chemoradiotherapy (CCRT) with cisplatin plus S-1 (SP) is commonly used for unresectable stage III non-small cell lung cancer (NSCLC) in clinical practice because of its favorable tolerability. However, evidence comparing SP with mitomycin C, vindesine, and cisplatin (MVP), the former standard therapy, is lacking. Methods Efficacy and safety of SP and MVP were compared in this target trial emulation study using data from eight Japanese randomized phase II and III CCRT trials. Confounding was adjusted using inverse probability of treatment weighting (IPTW) based on baseline clinical characteristics. Results The study population comprised 106 patients treated with SP and 145 treated with MVP. After IPTW adjustment, baseline characteristics were well balanced. SP therapy was associated with significantly prolonged progression-free survival (hazard ratio HR = 0.64, 95% confidence interval CI 0.42–0.98; p = 0.040) and time to treatment failure (HR 0.51, 95% CI 0.33–0.80; p = 0.002) compared with MVP, while overall survival showed a consistent but non-significant trend toward improvement (HR 0.68, 95% CI 0.43–1.07; p = 0.096). Objective response rates and disease control rates were comparable between groups. SP was associated with significantly lower incidences of grade ≥3 leukopenia, thrombocytopenia, neutropenia, febrile neutropenia, fatigue (all p < 0.001), and nausea ( p = 0.017), but a higher incidence of grade ≥3 diarrhea ( p = 0.008). Conclusions In patients with unresectable stage III NSCLC receiving CCRT, SP therapy demonstrated a trend toward greater efficacy compared with MVP, with favorable tolerability. These findings support SP as a clinically meaningful CCRT option.
Karayama et al. (Mon,) studied this question.