Immunotherapy with PD-1 inhibitors monotherapy or combined with chemotherapy comprises the first-line palliative treatment for patients with recurrent or metastatic head and neck squamous cell cancers (R/M HNSCC). The established survival advantage among responders is overshadowed by the high percentage of patients failing the standard PD-1 inhibitor-based treatments. Salvage therapies are direly needed. However, no current standards are available. We present the case of a 65-year-old patient with heavily pretreated laryngeal squamous cell carcinoma who had an exceptional response to cetuximab monotherapy following the failure of immunotherapy with the PD-1 inhibitor nivolumab. We reviewed the literature for other cases of exceptional response to cetuximab, clinical studies investigating the combined or sequential administration of cetuximab and PD-1 inhibitors, and the mechanistic rationale for consideration of cetuximab as a potential salvage treatment after immunotherapy with PD-1 inhibitors. In addition to the specific epidermal growth factor receptor inhibitory effect, cetuximab, as an immunoglobulin G1 isotype, binds NK cells and elicits antibody-dependent cellular toxicity, triggering a domino of immunostimulatory, and immunoinhibitory effects that actually might decrease the cetuximab anticancer efficacy. However, in a tumor microenvironment exposed to previous treatment with a PD-1 inhibitor, the effects of the PD-1 inhibitor followed by cetuximab on innate and adaptative immune response appear to synergize. Specifically, persistent immune checkpoint inhibitors' consequences may negate downstream immunosuppressive effects of cetuximab caused through PD-1/PD-L1 upregulation, making it a more potent treatment option. Besides the potential synergistic effect on antitumor immune response with previous immune checkpoint inhibitors therapy, cetuximab is the only targeted agent approved for treating R/M HNSCC, making it a most advantageous candidate for further treatment validation studies as salvage treatment post-immunotherapy.

中文翻译：

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转移性头颈鳞状细胞癌患者在检查点抑制剂免疫治疗失败后对西妥昔单抗单药治疗的特殊反应：病例报告和文献综述。

PD-1 抑制剂单药或联合化疗的免疫疗法是复发性或转移性头颈鳞状细胞癌 (R/M HNSCC) 患者的一线姑息治疗。应答者中既定的生存优势被基于标准 PD-1 抑制剂治疗的高比例患者失败所掩盖。迫切需要挽救疗法。然而，目前没有可用的标准。我们介绍了一名 65 岁喉鳞状细胞癌患者的病例，该患者在接受 PD-1 抑制剂纳武单抗免疫治疗失败后，对西妥昔单抗单药治疗产生了异常反应。我们回顾了西妥昔单抗特殊反应的其他病例的文献、调查西妥昔单抗和 PD-1 抑制剂联合或序贯给药的临床研究，以及考虑将西妥昔单抗作为 PD-1 抑制剂免疫治疗后潜在挽救治疗的机制原理。除了特定的表皮生长因子受体抑制作用外，西妥昔单抗作为免疫球蛋白 G1 同种型，还能结合 NK 细胞并引发抗体依赖性细胞毒性，引发多米诺骨牌免疫刺激和免疫抑制作用，实际上可能会降低西妥昔单抗的抗癌功效。然而，在先前接受过 PD-1 抑制剂治疗的肿瘤微环境中，PD-1 抑制剂和西妥昔单抗对先天性和适应性免疫反应的影响似乎具有协同作用。具体来说，持续性免疫检查点抑制剂的后果可能会抵消西妥昔单抗通过 PD-1/PD-L1 上调引起的下游免疫抑制作用，使其成为更有效的治疗选择。除了与先前的免疫检查点抑制剂治疗抗肿瘤免疫反应具有潜在的协同作用外，西妥昔单抗是唯一被批准用于治疗 R/M HNSCC 的靶向药物，使其成为进一步治疗验证研究的最有利候选药物，作为免疫治疗后的挽救治疗。