Efficacy and Safety of Pembrolizumab in the Treatment of Esophageal and Gastroesophageal Junction Cancer: A Meta-Analysis

Objectives: Several clinical trials have been conducted to investigate the safety and efficacy of pembrolizumab-containing therapy for esophageal cancer (EC) and gastroesophageal junction cancer (GEJC), but the outcomes vary greatly among studies and the optimal choice has not been identified. This study aimed to evaluate the efficacy and safety of pembrolizumab in the treatment of EC/GEJC by meta-analysis.Methods: PubMed, Embase, Web of Science and Cochrane library databases were searched to identify eligible studies (including single-arm studies or randomized controlled studies) of pembrolizumab for treating EC and GEJC updated to December 13, 2022. Primary outcomes including overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment related adverse events (TRAEs) were pooled using random-effect or fixed-effect models by considering of the heterogeneity. Meta-analysis was implemented using Stata statistical software.Results: A total of 8 clinical trials involving 1165 patients were enrolled. The pooled median OS time was 7.69 months (95% confidence interval (CI): 5.60, 9.79) for patients treated with pembrolizumab. The pooled rates of objective response, disease control and total TRAEs were 21.3% (95% CI: 9.9%, 35.3%), 48.9% (95% CI: 33.3%, 64.6%) and 78.5% (95% CI: 61.1%, 91.8%), respectively. Subgroup analysis indicated that pembrolizumab-based combination therapy tended to improve OS (8.74 vs. 7.14 months), ORR (39.1% vs. 12.8%) and DCR (66.7% vs. 37.6%) compared to pembrolizumab monotherapy, but there was no statistical significance (all p > 0.05). Notably, pembrolizumab monotherapy significantly decreased the rate of total TRAEs than combination therapy (67.1% vs. 90.1%,p = 0.033), mainly reflected on fatigue (18.0% vs. 45.6%), white blood cell decreased (0.7% vs. 30.4%), anorexia (8.8% vs. 36.5%), nausea (6.4% vs. 35.6%) and diarrhea (5.2% vs. 14.8%).Conclusion: Pembrolizumab was effective on clinical outcomes in the treatment of EC/GEJC, and individualized pembrolizumab is recommended on a clinical basis.