Brief Report: Real-World Comparative Effectiveness of First-Line Immune Checkpoint Inhibitor Monotherapy Versus Chemo-Immunotherapy in Metastatic NSCLC With PD-L1 More Than or Equal to 50%: A Meta-Analysis

Introduction: For patients with metastatic NSCLC and high PD-L1 expression (≥50%), both immune checkpoint inhibitor (IO) monotherapy and chemo-immunotherapy (chemo-IO) are established first-line options. Although randomized trials have suggested similar overall survival (OS) between these strategies, real-world outcomes-especially in clinically heterogeneous populations-remain poorly defined. Methods: A systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines was conducted. Eligible studies were retrospective comparative cohorts evaluating first-line IO monotherapy versus chemo-IO in adults with metastatic NSCLC and PD-L1 more than or equal to 50%. Primary outcome was OS; secondary outcomes included progression-free survival and objective response rate. Hazard ratios (HRs) were pooled using random-effects models. Results: A total of 19 retrospective studies comprising 11,048 patients were included (3337 chemo-IO; 7711 IO monotherapy). Chemo-IO significantly improved objective response rate (60% versus 41%). Pooled analyses demonstrated a benefit for chemo-IO in progression-free survival (HR = 0.75, 95% confidence interval [CI]: 0.67-0.85) and OS (HR = 0.82, 95% CI: 0.75-0.90). Subgroup analyses revealed marked heterogeneity: OS benefit of chemo-IO was pronounced in patients with Eastern Cooperative Oncology Group performance status of 0 (HR = 0.45, 95% CI: 0.32-0.63), in never-smokers (HR = 0.35, 95% CI: 0.17-0.70), and in women (HR = 0.68, 95% CI: 0.58-0.80). No significant OS advantage was observed in patients with PS more than or equal to 2 or age more than or equal to 75 years. Conclusions: In real-world practice, chemo-IO provides potential clinical benefit than IO monotherapy in PD-L1-high metastatic NSCLC, although the magnitude varies by patient characteristics. Ongoing prospective trials are essential to refine treatment selection and identify patients for whom chemotherapy can be safely omitted.