Immunotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of randomized clinical trials

Locoregionally advanced nasopharyngeal carcinoma (LANPC) is the predominant stage at diagnosis and is commonly treated with cisplatin-based chemoradiotherapy (CRT). Although this approach achieves excellent locoregional control, distant metastasis remains the leading cause of treatment failure. Immunotherapy with programmed cell death protein 1 (PD-1) inhibitors, supported by the immunogenicity of Epstein-Barr virus-associated disease, has emerged as a promising strategy.

To synthesize evidence from phase III trials on the efficacy and safety of PD-1 blockade combined with definitive chemoradiotherapy in LANPC.

Systematic review and meta-analysis of randomized controlled trials.

We systematically searched for phase III randomized controlled trials evaluating PD-1 blockade plus chemoradiotherapy versus chemoradiotherapy (with or without placebo) in previously untreated LANPC. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted for event-/failure-free survival (EFS/FFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Pooled effects were estimated with random-effects models, with heterogeneity assessed using I² and prediction intervals. Safety outcomes were summarized descriptively.

Three trials including 1237 patients were identified. PD-1 blockade significantly improved EFS/FFS (HR 0.66, 95% CI: 0.49-0.89; I² = 18.6%; prediction interval 0.46-0.96), with the greatest effect on DMFS (HR 0.61, 95% CI: 0.43-0.85; I² = 0%). LRFS showed a nonsignificant trend toward benefit (HR 0.67, 95% CI: 0.41-1.11; I² = 43.6%), though a clear advantage was evident in cisplatin-based regimens (HR 0.53, 95% CI: 0.34-0.82). OS data were immature (HR 0.94, 95% CI: 0.60-1.48; I² = 0%). Rates of severe and fatal adverse events were comparable between groups.

This first meta-analysis of phase III evidence demonstrates that PD-1 blockade combined with cisplatin-based chemoradiotherapy improves disease control in LANPC without added toxicity. Longer follow-up from ongoing studies is needed to establish the OS benefit and optimize treatment strategies.

PROSPERO CRD-420251147756.