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

Abstract

Abstract 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.

Keywords

• S-1
• Vinorelbine
• Pemetrexed
• Docetaxel
• Locally advanced non-small-cell lung cancer
• IPD meta-analysis