Safety of pembrolizumab in advanced head and neck squamous cell carcinoma: A systematic review and meta-analysis of RCTs

Abstract

Background: Pembrolizumab, a checkpoint inhibitor, has demonstrated safety and efficacy in various cancers, primarily melanomas and non-small cell lung cancers. However, its safety profile in Head and Neck Squamous Cell Carcinoma (HNSCC) remains inadequately studied. This meta-analysis aims to evaluate adverse events (AEs) associated with pembrolizumab in patients with advanced HNSCC. Method(s): A systematic search was conducted using PubMed, Embase, Cochrane Library, Web of Science, and clinicaltrials.gov. Randomized controlled trials (RCTs) evaluating pembrolizumab monotherapy in patients with advanced HNSCC were included. Primary outcomes included overall AEs, grade 3-5 AEs, immune-related AEs, and treatment discontinuation due to AEs. Random effects models were used for analysis. Statistical analysis was performed using Review Manager 5.4 (RevMan). A p-value <= 0.05 was considered statistically significant. Result(s): A total of 1,900 patients (mean age: 59.86 +/- 9.1 years; females: 16.73%) with advanced HNSCC were included from three RCTs. Patients receiving pembrolizumab monotherapy had higher odds of experiencing overall AEs (OR 2.00, 95% CI 1.04-3.83, p = 0.04), grade 3-5 AEs (OR 1.13, 95% CI 0.68-1.86, p = 0.63), immune-related AEs (OR 1.49, 95% CI 0.44-5.08, p = 0.53), and lower odds of treatment discontinuation due to AEs (OR 0.77, 95% CI 0.34-1.75, p = 0.53) compared to the control group. However, only overall AEs were statistically significant. Conclusion(s): Pembrolizumab is associated with a higher risk of AEs in patients with advanced HNSCC compared to the control group. Interestingly, the likelihood of treatment discontinuation due to AEs was lower in the pembrolizumab group; however, this difference was not statistically significant. Further research, including larger RCTs with longer follow-up periods, is necessary to evaluate the safety profile of pembrolizumab in patients comprehensively. Additionally, studies should focus on identifying specific patient subgroups at greater risk for AEs and exploring strategies to mitigate these risks.