免疫治疗时代转移性鼻咽癌的系统治疗：一篇批判性综述。

文献信息

中文摘要

背景： 尽管局部区域治疗和系统治疗近期取得了进展，转移性鼻咽癌（mNPC）的预后仍然很差。将程序性死亡-1（PD-1）抑制剂纳入一线化疗已改变了治疗格局；然而，在初始化疗-免疫治疗之后的最佳治疗策略仍未明确。
方法： 我们对评估免疫治疗时代mNPC系统治疗的前瞻性临床试验、大型回顾性研究和转化研究进行了批判性综述，重点关注治疗顺序和临床决策。
结果： 多项III期试验已确立吉西他滨-顺铂联合PD-1阻断作为复发或转移性鼻咽癌的标准一线治疗，成熟随访现已证明持久的总生存获益可达5年。后续治疗选择包括细胞毒性化疗、抗血管生成药物、抗体-药物偶联物（ADC）和免疫治疗再挑战策略。其中，VEGF靶向联合方案和EGFR/HER3导向的ADC在PD-1耐药疾病中显示出最有前景的活性，尽管不同方案的毒性特征和缓解持久性各异。
结论： mNPC的治疗范式正在迅速演变，超越一线化疗-免疫治疗。新出现的证据支持基于生物学信息的治疗选择，纳入血管生成抑制、ADC和免疫调节。迫切需要针对最佳顺序、预测性生物标志物以及系统治疗与局部治疗整合的前瞻性试验。

英文摘要

BACKGROUND: The prognosis of metastatic nasopharyngeal carcinoma (mNPC) remains dismal despite recent advances of locoregional and systemic therapy. The incorporation of programmed death-1 (PD-1) inhibitors into first-line chemotherapy has transformed the therapeutic landscape; however, optimal treatment strategies beyond initial chemo-immunotherapy remain undefined.
METHODS: We conducted a critical review of prospective clinical trials, large retrospective studies, and translational research evaluating systemic therapies for mNPC in the immunotherapy era, with a focus on treatment sequencing and clinical decision-making.
RESULTS: Multiple phase III trials have established gemcitabine-cisplatin combined with PD-1 blockade as the standard first-line treatment for recurrent or metastatic NPC, with mature follow-up now demonstrating durable overall survival benefits reaching up to 5 years. Subsequent-line treatment options include cytotoxic chemotherapy, anti-angiogenic agents, antibody-drug conjugates (ADCs), and immunotherapy rechallenge strategies. Among these, VEGF-targeted combinations and EGFR/HER3-directed ADCs have demonstrated the most promising activity in PD-1-resistant disease, although toxicity profiles and durability of response vary across regimens.
CONCLUSIONS: The treatment paradigm for mNPC is rapidly evolving beyond first-line chemo-immunotherapy. Emerging evidence supports biologically informed treatment selection incorporating angiogenesis inhibition, ADCs, and immune modulation. Prospective trials addressing optimal sequencing, predictive biomarkers, and integration of systemic and local therapies are urgently warranted.