Immune checkpoint inhibitor integration in locoregionally advanced nasopharyngeal carcinoma: a prospective evidence synthesis on efficacy, safety, and therapeutic optimization.

Background: Several prospective and randomized trials support immune checkpoint inhibitors (ICIs) as an emerging component of standard definitive treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). The key uncertainty has shifted from whether ICIs have antitumor activity to how they should be incorporated into multimodality therapy, including therapeutic modality, treatment timing, chemotherapy backbone, treatment duration, and agent selection. Methods: We performed a pooled analysis of seven prospective trials enrolling 1,788 patients with LA-NPC, with data retrieved through December 2025. ICI-based regimens were evaluated across four prespecified dimensions: therapeutic modality, immunotherapy timing, chemotherapy backbone, and individual ICI agent. The protocol was registered with PROSPERO (CRD420261293069). Results: Seven prospective trials involving 1788 patients were included. ICI-containing strategies were associated with high pooled survival estimates, including 3-year overall survival (OS) of 96.4% and 3-year failure-free survival (FFS) of 88.2%. Exploratory strategy-level analyses suggested clinically relevant differences across ICI integration approaches. In the neoadjuvant setting, chemoimmunotherapy plus antiangiogenic therapy showed the highest complete response (CR) estimate (26.5%) but also the highest grade 3 or higher treatment-related adverse event estimate (65.3%); ICI monotherapy showed limited neoadjuvant activity, with a CR estimate of 1.0%. For treatment sequencing, neoadjuvant-adjuvant ICI administration showed favorable long-term disease-control estimates, including 3-year locoregional recurrence-free survival of 96.0% and 3-year OS of 99.0%, whereas full-course neoadjuvant-concurrent-adjuvant ICI administration was associated with the lowest progressive disease estimate (0.2%). Chemotherapy backbone also appeared relevant: modified taxane-platinum-fluoropyrimidine showed a higher neoadjuvant CR estimate than gemcitabine-cisplatin (31.4% vs 13.7%). At the agent level, camrelizumab-based regimens achieved neoadjuvant objective response of 100.0%, although with a higher immune-related adverse event estimate (81.8%); toripalimab-based regimens showed 3-year OS of 97.0% with a lower overall immune-related adverse event estimate (53.6%). Conclusion: ICI-containing strategies showed favorable current survival estimates and measurable tumor activity in LA-NPC; however, their clinical relevance appears to vary according to how ICIs are integrated into multimodality treatment. Given that several strategy-level estimates were based on few heterogeneous studies and relatively short follow-up, these findings should be viewed as hypothesis-generating and used to inform treatment optimization and future randomized, biomarker-informed trials, rather than to identify a single preferred ICI strategy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261293069, identifier CRD420261293069.