Real-world meta-analysis supports pembrolizumab for advanced NSCLC with high PD-L1

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Annals of surgical oncology Published May 3, 2026 Medically reviewed May 8, 2026 Study authors: Machado Guilherme Franceschini, Grillo Iago T C, D'ambrosio Paula Duarte, Romao Victoria Trasatti, R… PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider real-world evidence supporting pembrolizumab for advanced NSCLC with high PD-L1, noting observational limitations.

This systematic review and meta-analysis synthesized real-world evidence on first-line pembrolizumab monotherapy for patients with advanced non-small cell lung cancer and PD-L1 expression of 50% or greater, excluding those with EGFR or ALK alterations. The analysis pooled data from multiple observational studies to assess overall survival, progression-free survival, and adverse events.

The authors observed improvements in pooled mean overall survival and progression-free survival. They also noted a modest long-term survival rate at five years. Safety data indicated that adverse events were common but serious events were less frequent. Subgroup analyses suggested that older age and poorer performance status were associated with worse outcomes, while PD-L1 expression and brain metastases did not show significant differences.

Key limitations include the observational design of the included studies, which precludes causal inference, and the reliance on reconstructed survival curves for pooled estimates. The certainty of the evidence depends on the quality of the real-world data. The authors caution against extrapolating beyond the specified PD-L1 population.

Clinically, this real-world evidence supports the effectiveness and safety of pembrolizumab monotherapy in routine practice for eligible patients. However, clinicians should interpret these findings in the context of the study limitations and avoid overstating causality.

Study Details

Study typeMeta analysis

Sample sizen = 17,506

EvidenceLevel 1

Follow-up21.0 mo

PublishedMay 2026

PMID41644920

View Original Abstract ↓

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.