Real-World Long-Term Outcomes of First-Line Pembrolizumab in Advanced PD-L1 ≥ 50% NSCLC: A Systematic Review and Meta-analysis

Background Pembrolizumab monotherapy is the standard first-line treatment for advanced non-small-cell lung cancer (NSCLC) with programmed cell death ligand-1 (PD-L1) expression ≥ 50%. However, long-term effectiveness and safety in real-world populations remain underexplored. Methods We systematically searched PubMed, Embase, and the Cochrane Library through February 2025 for real-world studies reporting outcomes of first-line pembrolizumab monotherapy in patients with advanced NSCLC and PD-L1 ≥ 50%, excluding those with EGFR/ALK alterations. Primary outcomes were pooled mean overall survival (OS), timepoint-specific OS rates, and progression-free survival. Secondary outcomes included adverse event rates and hazard ratios (HRs) for OS based on age, Eastern Cooperative Oncology Group performance status, PD-L1 intensity, and brain metastases. Kaplan–Meier curves were digitally reconstructed using R. Results In total, 12 studies encompassing 17,506 patients were included. The pooled mean OS was 21.0 months (95% confidence interval [CI] 16.9–25.1), and the 60-month OS rate was 29.0%. Mean progression-free survival was 8.7 months (95% CI 6.3–11.0). Any-grade and grade ≥3 adverse events occurred in 52% and 12% of patients, respectively. Age ≥70 years was associated with worse OS (HR 1.26; 95% CI 1.23–1.29). Eastern Cooperative Oncology Group status ≥2 was also linked to poorer outcomes (HR 2.05; 95% CI 1.04–4.05). No significant OS difference was observed for PD-L1 or brain metastases. Conclusions Real-world evidence confirms the long-term effectiveness and safety of pembrolizumab monotherapy for advanced NSCLC with PD-L1 ≥50%. Survival outcomes closely mirrored those from previous trials, supporting the generalizability of pembrolizumab’s benefit across routine practice.