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Pembrolizumab combined with chemotherapy for advanced or metastatic non-small cell lung cancer with low PD-L1 expression: a systematic review and meta-analysis of randomized controlled trials.

Created on 28 Apr 2026

Authors

Akhil Deepak Vatvani, Gilbert Lazarus, Reyad Al Jabiri, Rama Nada, Maria Albuja Altamirano, Eunhee Choi, Nehad Shabarek

Published in

Immunotherapy. Pages 1-11. Apr 27, 2026. Epub Apr 27, 2026.

Abstract

Pembrolizumab plus chemotherapy is widely used as first-line treatment for advanced NSCLC, but its benefit in patients with low PD-L1 expression remains uncertain. This study evaluated pembrolizumab plus chemotherapy versus chemotherapy alone in advanced or metastatic NSCLC with PD-L1 <50%.
PubMed, Scopus, and Cochrane databases were searched for randomized controlled trials up to 17 September 2025. Primary outcomes were overall survival (OS) and progression-free survival (PFS).
Four randomized controlled trials (n = 2,413) were included. Pembrolizumab plus chemotherapy improved overall survival (HR 0.67, 95% CI 0.46-0.96), while progression-free survival showed a non-significant trend (HR 0.66, 95% CI 0.42-1.03). Subgroup analyses by PD-L1 (<1% and 1-49%) showed borderline, non-significant effects. Objective response rate was higher overall (RR 1.75, 95% CI 1.13-2.70) but not significant by subgroup, with moderate heterogeneity. Certainty of evidence was low. Safety outcomes were not pooled; available data suggested similar adverse events but higher immune-related toxicity and numerically higher treatment-related deaths.
Pembrolizumab plus chemotherapy may improve survival in advanced NSCLC with low PD-L1 expression, but benefits were inconsistent across subgroups and limited by imprecision and heterogeneity. Safety data remain limited and should be interpreted cautiously.

PMID:
42046364
Bibliographic data and abstract were imported from PubMed on 28 Apr 2026.

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