Adverse effects associated with immune checkpoint inhibitors in locally advanced nasopharyngeal carcinoma: A meta-analysis of randomized controlled trials.

Abstract

e18105 Background: Immune checkpoint inhibitors (ICIs) are increasingly incorporated into curative-intent treatment strategies for locally advanced nasopharyngeal carcinoma (LA NPC), either with concurrent chemoradiation or following induction chemotherapy. While early efficacy results are promising, the toxicity profile of these combinations remains clinically relevant. We conducted a meta-analysis to characterize adverse events associated with the addition of ICIs to standard therapy in LA NPC. Methods: MEDLINE and EMBASE were systematically searched through January 10, 2026 to identify phase II and III randomized controlled trials evaluating ICIs added to standard therapy for LA NPC. Adverse events of interest included immune-related adverse events (irAEs), locoregional toxicities, general and hematologic adverse events, late adverse events, and serious treatment-related adverse events. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a fixed-effects inverse variance model. Heterogeneity was assessed using Cochran’s Q and I² statistics. Results: Two randomized trials including 572 patients met inclusion criteria. Compared with standard therapy alone, ICI-containing regimens were associated with significantly higher rates of immune-related adverse events. The pooled RR for any-grade irAEs was 10.71 (95% CI: 6.43–17.85; p<0.00001), with a corresponding increase in high-grade irAEs (RR 25.82; 95% CI: 8.35–173.38; p=0.0008). Hypothyroidism (any grade, predominantly grade 1–2) was more frequent with ICIs (RR 7.89; 95% CI: 4.11–15.16; p<0.00001). Cutaneous toxicities were also increased, including rash (any grade RR 16.13; 95% CI: 6.20–41.95; p<0.00001; high grade RR 13.28; 95% CI: 1.86–94.98; p=0.01) and pruritus (any grade RR 22.18; 95% CI: 7.04–69.85; p<0.00001). In contrast, rates of locoregional toxicities, hematologic adverse events, late adverse events, serious treatment-related adverse events, and treatment-related mortality were similar between groups. Conclusions: In locally advanced nasopharyngeal carcinoma, the addition of immune checkpoint inhibitors to standard therapy increases immune-related adverse events, largely low grade, without a corresponding increase in locoregional, hematologic, or late toxicities. These findings support the overall tolerability of ICI-containing regimens in LA NPC with appropriate monitoring.