Concurrent chemoradiotherapy with cisplatin + S-1 versus cisplatin + other third-generation agents for locally advanced non-small-cell lung cancer: a meta-analysis of individual participant data

BACKGROUND: For decades, concurrent chemo-radiotherapy with cisplatin-based regimen has been a standard therapy for locally advanced stage III non-small-cell lung cancer (NSCLC). We conducted individual-participant-data (IPD) meta-analyses to compare S-1/cisplatin versus other third-generation anti-cancer medications plus cisplatin regimens with the goal of determining whether or not S-1/cisplatin was the ideal choice for treatment accompanied by radiotherapy (RT). METHODS: A thorough search was performed using multiple electronic databases. We integrated the IPD of each trial and analyzed the resulting meta-database. The primary endpoint was the overall survival (OS), and the secondary endpoints included the progression-free survival (PFS), objective response rate (ORR), toxicities, and treatment delivery. Subgroup analyses were conducted based on baseline characteristics. Statistical analyses were stratified by trials. RESULTS: Three randomized control trials (WJOG5008L study, SPECTRA study, and TORG1018 study) were found. Of the 316 patients enrolled in those studies, 159 received S-1/cisplatin (SP), and 157 were assigned to other combination chemotherapy. The median OS for the SP arm was 48.2 months, and that of the non-SP arm was 42.4 months. The combined hazard ratio (HR) for the OS was 0.895 (95% confidence interval [CI] 0.638–1.256), and no heterogeneity was noted among the trials (test for heterogeneity, p = 0.87; I(2) = 0). The median PFS for the SP and non-SP arms was 12.8 and 14.0 months, respectively. The corresponding HR for the PFS was 1.022 (95% CI 0.776–1.347), and there was evidence of moderate heterogeneity among the trials (test for heterogeneity, p = 0.16; I(2) = 0.46). The ORRs were 69.7% (95% CI 62.1–76.7%) and 70.9% (95% CI 63.7–78.1%) in the SP and non-SP arms, respectively. The toxicity profile showed that SP caused significantly fewer instances of grade 3–4 leukopenia and neutropenia than non-SP regimens. CONCLUSION: No marked differences were detected in the OS, PFS, or ORR between the SP and non-SP arms. SP had significantly less myelosuppression and better treatment compliance as a chemotherapy regimen for concurrent chemoradiation in locally advanced NSCLC than non-SP regimens. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-022-01828-z.