Comparison of long-term survival between nivolumab plus ipilimumab with chemotherapy and pembrolizumab with chemotherapy in advanced non-small cell lung cancer: A multicenter retrospective cohort study

BACKGROUND: Nivolumab plus ipilimumab with chemotherapy (NICT) and pembrolizumab with chemotherapy (PCT) are widely used first-line regimens for advanced non-small-cell lung cancer (NSCLC) lacking actionable driver mutations. However, real-world evidence comparing long-term survival outcomes between two regimens, particularly when stratified by PD-L1 tumor proportion score (TPS), remains limited. METHODS: We retrospectively analyzed 457 patients treated with NICT or PCT across 13 institutions in Japan between January 2019 and December 2022. Patients were classified into PD-L1 TPS < 1% and ≥ 1% cohorts. Overall survival (OS) and treatment-related adverse events (TRAEs) were assessed using propensity score methods, including inverse probability treatment weighting (IPTW) and overlap weighting (OW), adjusting for 10 clinically relevant covariates. RESULTS: The duration of median follow-up exceeded 40 months. Among 161 patients with PD-L1 TPS < 1% (NICT n = 43; PCT n = 118), NICT achieved significantly longer OS than PCT (median 47.4 versus 16.6 months; IPTW-adjusted hazard ratio 0.50; p = 0.007), with superior 36-month OS rates (51.5% versus 28.2%; p = 0.016). These trends remained robust in the OW sensitivity analysis. In contrast, among 296 patients with PD-L1 TPS ≥ 1% (NICT n = 45; PCT n = 251), no significant differences were observed in median OS or 36-month OS rates between regimens. Grade ≥ 3 TRAEs, treatment discontinuation, and treatment-related death rates were comparable (p = 0.37, 0.78, and 0.32, respectively). CONCLUSIONS: NICT provides a sustained long-term survival advantage over PCT with comparable tolerability and may be a promising therapeutic option for the treatment of advanced NSCLC that are PD-L1 negative.