PD-1/PD-L1抑制剂联合抗血管生成酪氨酸激酶抑制剂治疗复发或转移性鼻咽癌的疗效与安全性：系统评价与单臂荟萃分析

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中文摘要

目的： 评估PD-1/PD-L1抑制剂联合小分子抗血管生成药物（阿帕替尼、安罗替尼和法米替尼）治疗复发/转移性鼻咽癌（R/M NPC）的疗效与安全性。
方法： 系统检索截至2026年1月7日的主要数据库，纳入PD-1/PD-L1抑制剂联合阿帕替尼、安罗替尼或法米替尼治疗R/M NPC的前瞻性单臂II期试验以及回顾性队列/真实世界研究。采用随机效应模型估计合并缓解率和安全性率，并使用适当工具评估研究质量。
结果： 共纳入9项研究，包含10个独立队列（357例患者）。合并客观缓解率（ORR）为48%（95% CI：39%-57%），疾病控制率（DCR）为83%（95% CI：77%-88%），1年总生存率为79%（95% CI：68%-86%）。≥3级治疗相关不良事件（TRAEs）的发生率为47%（95% CI：37%-58%）。最常见的严重TRAEs为高血压（9%）、手足综合征（10%）和鼻咽坏死（14%），后者因可能导致严重出血并发症而需要密切监测。所有纳入研究中均未报告治疗相关死亡。亚组分析显示，卡瑞利珠单抗与特瑞普利单抗之间的ORR无显著差异；阿帕替尼的ORR高于安罗替尼；免疫治疗初治患者的ORR显著高于既往接受过免疫检查点抑制剂（ICIs）治疗的患者（p = 0.0028）。
结论： 该联合方案在R/M NPC中显示出有前景的抗肿瘤活性和总体可接受的安全性，尤其对于免疫治疗初治患者。这些发现支持在精心设计的随机对照试验中进一步研究，但其相对于标准治疗的作用仍需更大规模的比较研究来确认。

英文摘要

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.