Safety and efficacy of pembrolizumab plus lenvatinib as first-line therapy in non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials.

e20634 Background: Pembrolizumab, an anti-PD-1 antibody, and Lenvatinib, a multi-kinase inhibitor, were identified as potentially effective treatment agents for various malignancies, including non-small cell lung cancer (NSCLC). Prior research indicated that the combination of these two drugs may significantly enhance survival outcomes compared to conventional treatments. Nevertheless, the safety and efficacy of Pembrolizumab plus Lenvatinib as first-line treatment for NSCLC remain uncertain. This study aims to evaluate the therapeutic effects and possible risks of this combination therapy in patients with NSCLC by assessing outcomes, including overall survival, progression-free survival, and adverse events. Methods: Following PRISMA guidelines and registration with PROSPERO, databases including PubMed, the Cochrane Library, EMBASE, and ClinicalTrials.gov were searched from inception to January 2026 for studies evaluating the efficacy and safety of Pembrolizumab plus Lenvatinib in patients with NSCLC undergoing first-line therapy. Data were analyzed using RevMan version 5.4 with a random-effects model to estimate pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals. A p-value < 0.05 was considered statistically significant. Results: Six studies (n = 2,164) assessed the efficacy and safety of Pembrolizumab plus Lenvatinib in patients with NSCLC receiving first-line therapy. The combination treatment significantly reduced the risk of progression by 15% (HR 0.85; 95% CI 0.76–0.95; p = 0.005), though no significant difference in overall survival was observed (HR 1.05; 95% CI 0.93–1.18; p = 0.42). Pembrolizumab plus Lenvatinib also demonstrated a 30% higher overall response rate (RR 1.30; 95% CI 1.08–1.57; p = 0.005), with moderate heterogeneity (I² = 49%). However, this treatment was associated with an increased risk of grade 3-5 treatment-related adverse events (TRAEs) (RR 1.41; I² = 90%) and a higher risk of TRAEs, which leads to discontinuation (RR 1.81) and death (RR 2.39). Conclusions: Pembrolizumab plus Lenvatinib as first-line treatment in patients with NSCLC showed potentially effective therapeutic benefits by significantly lowering the risk of progression and increasing the overall response rate. Conversely, the combination is correlated with an increased risk of TRAEs of grade 3-5, accompanied by a higher probability of TRAEs leading to discontinuation and death. Future studies with large sample sizes are needed to validate these results and provide insight of risk-to-benefit ratio of this combined therapy