Efficacy and safety of immune checkpoint inhibitors in recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis.

e14612 Background: Treatment options for recurrent or metastatic nasopharyngeal carcinoma (NPC) are limited. Recently, the introduction of Immune Checkpoint Inhibitors (ICIs), either as single agents or combined with other treatment options, has emerged as a potential treatment for NPC. Hence, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICIs compared to standard chemotherapy. Methods: We systematically searched PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing ICIs versus standard chemotherapy in patients with NPC. The main outcomes were progression-free survival (PFS), overall survival (OS) and adverse events rate. All analyses used a random-effects model, with 95% confidence intervals (CIs) and were conducted on Review Manager 5.4. Results: A total of 1,188 patients from 5 RCTs were included, of which 634 (53.3%) received PD-1 inhibitors. In a pooled analysis of all studies, treatment with ICIs demonstrated a statistically significant benefit in OS (HR 0.73; 95% CI 0.61-0.87; p<0.01). In trials evaluating ICI monotherapy versus chemotherapy (617 patients), PFS was not significantly different between groups (p=0.91). However, pooling two studies evaluating ICI combined with chemotherapy vs. chemotherapy (541 patients) demonstrated higher PFS for the ICI group (HR 0.53; 95% CI 0.42-0.67; p<0.01). Overall pooled PFS was non-significant (HR 0.75; 95% CI 0.49-1.16; p=0.20). In all subgroup analyses, patients treated with ICI achieved greater PFS than chemotherapy: low EBV DNA level (HR 0.61; 95% CI 0.42-0.87; p=0.007) or high EBV DNA level (HR 0.44; 95% CI 0.35-0.56; p<0.01), without liver metastasis (HR 0.68; 95% CI 0.47-0.98; p=0.04), and with liver metastasis (HR 0.56; 95% CI 0.38-0.83; p=0.04). Moreover, ICIs were well tolerated and not associated with an increased risk of serious adverse events (HR 0.96; 95% CI 0.82-1.11; p=0.56). The frequency of hypothyroidism increased in the ICI group (HR 2.07; 95% CI 1.63-2.63; p<0.01). Other adverse events had similar rates in both groups, such as AST and ALT levels, diarrhea, pruritus, rash, stomatitis, and vomiting. Conclusions: This meta-analysis demonstrated that immune checkpoint inhibitors significantly enhanced overall survival without substantially increasing serious adverse events in patients with M/R NPC. Further studies are needed to identify the patients who benefit the most from ICI monotherapy or combination therapies. [Table: see text]