Efficacy and Safety of PD ‐1/ PD ‐ L1 Inhibitors Combined With Anti‐Angiogenic Tyrosine Kinase Inhibitors for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Systematic Review and Single‐Arm Meta‐Analysis

ABSTRACT Objective To evaluate the efficacy and safety of PD‐1/PD‐L1 inhibitors plus small‐molecule anti‐angiogenic drugs (apatinib, anlotinib and famitinib) for recurrent/metastatic nasopharyngeal carcinoma (R/M NPC). Methods Systematic searches of major databases up to January 7, 2026 identified prospective single‐arm Phase II trials and retrospective cohort/real‐world studies of PD‐1/PD‐L1 inhibitors combined with apatinib, anlotinib, or famitinib in R/M NPC. Pooled response and safety rates were estimated using random‐effects models, with study quality assessed by appropriate tools. Results Nine studies comprising 10 independent cohorts (357 patients) were included. The pooled objective response rate (ORR) was 48% (95% CI: 39%–57%), the disease control rate (DCR) 83% (95% CI: 77%–88%), and the 1‐year overall survival rate 79% (95% CI: 68%–86%). The incidence of grade ≥ 3 treatment‐related adverse events (TRAEs) was 47% (95% CI: 37%–58%). The most frequent serious TRAEs were hypertension (9%), hand‐foot syndrome (10%), and nasopharyngeal necrosis (14%), with the latter requiring close monitoring due to its potential for severe bleeding complications. No treatment‐related deaths were reported across all included studies. Subgroup analysis showed no significant difference in ORR between camrelizumab and toripalimab; apatinib yielded higher ORR than anlotinib; immunotherapy‐naive patients had significantly higher ORR than those previously treated with immune checkpoint inhibitors (ICIs) ( p  = 0.0028). Conclusion The combination shows promising antitumor activity and a generally acceptable safety profile in R/M NPC, particularly for immunotherapy‐naive patients. These findings support further investigation in well‐designed randomized controlled trials, but confirmation of its role relative to standard therapies requires larger comparative studies.