INTRODUCTION: 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%. METHODS: 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). RESULTS: = 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. CONCLUSIONS: 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.
Vatvani et al. (2026) studied this question.