Background: Recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) after immune checkpoint inhibitor (ICI) progression represents a major clinical challenge. Between 60 and 80% of patients develop resistance, and historical salvage regimens like cytotoxic chemotherapy or chemotherapy plus cetuximab rarely extend median overall survival (mOS) beyond one year. Scope of Review: This review examines systemic therapies evaluated specifically in the post-ICI setting, emphasizing agents advancing to Phase II and III trials. Classes include chemotherapy combinations, ICI-based approaches, small-molecule targeted combinations, bispecific antibodies, antibody-drug conjugates (ADCs), and next-generation vaccines. Results: Promising signals have emerged across multiple therapeutic modalities. Targeted combination strategies have demonstrated encouraging response rates and survival outcomes in difficult-to-treat, PD-1-resistant disease. Antibody-based platforms, including antibody-drug conjugates and bispecific antibodies, continue to show consistent clinical activity across diverse patient populations, offering disease control and prolonged survival. Novel immunotherapies and therapeutic vaccines are also generating durable responses, particularly in biologically defined subgroups, highlighting the potential of immune-based precision treatments in R/M HNSCC. Conclusions: Comparative analysis highlights distinct advantages and limitations: chemotherapy ensures rapid shrinkage but poor durability; biomarker-driven small molecules achieve strong survival gains in narrow niches; ADCs and bispecifics offer balanced efficacy in unselected patients; and vaccine platforms deliver durable benefit in defined subsets. Together, these data signal a paradigm shift toward biomarker-guided, mechanism-driven strategies as the path to closing the post-ICI therapeutic gap in R/M HNSCC.
背景：免疫检查点抑制剂（ICI）进展后的复发性和转移性头颈部鳞状细胞癌（R/M HNSCC）是临床面临的主要挑战。60%至80%的患者会产生耐药性，而传统的挽救性方案如细胞毒性化疗或化疗联合西妥昔单抗，其中位总生存期（mOS）很少能延长超过一年。综述范围：本综述专门探讨了在ICI治疗后评估的系统性疗法，重点关注已进入II期和III期试验的药物。类别包括化疗联合方案、基于ICI的策略、小分子靶向联合疗法、双特异性抗体、抗体药物偶联物（ADCs）以及新一代疫苗。结果：多种治疗模式均显示出有希望的信号。靶向联合策略在难治性、PD-1耐药的疾病中表现出令人鼓舞的缓解率和生存结局。基于抗体的平台，包括抗体药物偶联物和双特异性抗体，在不同患者群体中持续显示出稳定的临床活性，提供了疾病控制和生存期延长的可能。新型免疫疗法和治疗性疫苗也正在产生持久的应答，特别是在生物学定义的亚组中，凸显了基于免疫的精准治疗在R/M HNSCC中的潜力。结论：比较分析突出了各自的优势和局限性：化疗能确保快速缩小肿瘤但持久性差；生物标志物驱动的小分子药物在特定狭窄人群中实现了显著的生存获益；抗体药物偶联物和双特异性抗体在未经筛选的患者中提供了均衡的疗效；而疫苗平台在特定亚组中带来了持久的益处。这些数据共同标志着，向生物标志物引导、机制驱动的策略转变，是填补R/M HNSCC在ICI治疗后治疗空白的关键路径。
肿瘤(癌症)患者之家