Comparative efficacy of chemo-immunotherapy combination regimens in the frontline setting for NSCLC based on reconstructed patient data

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of metastatic NSCLC and have become standard first-line therapy both as monotherapy, for patients with PD-L1 expression ≥50%, and in combination with chemotherapy (CT), regardless of PD-L1 expression. This study used an artificial intelligence technique, the IPDfromKM method, to reconstruct individual patient data from Kaplan-Meier curves of phase III randomised clinical trial results to provide a comparative overview of different first-line chemo-immunotherapy options. Overall survival (OS) was estimated using hazard ratios and restricted mean survival time (RMST). Ten clinical trials were included in the analysis. In the squamous population, combinations of cemiplimab + CT (HR = 0.56), pembrolizumab + CT (HR = 0.67), and nivolumab + ipilimumab + CT (HR = 0.71) significantly improved OS compared with CT alone, with no difference between treatments. At longer follow-up, nivolumab + ipilimumab + CT showed longer RMST compared to pembrolizumab + CT in the PD-L1 < 1% subgroup (24.9 months vs. 22.8 months). In non-squamous NSCLC, the survival benefit of ICIs + CT was much more homogeneous, with similar results across the different options. Overall, pembrolizumab + CT showed the best results both in terms of HR (0.68, 95%CI 0.60-0.77) and RMST at long follow-up (30.4 months in the PDL-1 ≥ 1% subgroup and 24 months in the PDL-1 < 1% population). In conclusion, there are some differences between frontline options for treating metastatic NSCLC based on tumour histology and PD-L1 expression. However, further head-to-head trials and longer follow-up are needed to clarify the clinical impact of these differences.