Abstract / Summary
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.