Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, California, USA.
Expert Opin Emerg Drugs. 2022 Sep;27(3):333-344. doi: 10.1080/14728214.2022.2125954. Epub 2022 Sep 21.
Conventional regimens for head and neck squamous cell carcinoma (HNSCC) are limited in efficacy and are associated with adverse toxicities. Food and Drug Administration (FDA) approved molecular targeting agents include the HER1 (EGFR)-directed monoclonal antibody cetuximab and the immune checkpoint inhibitors nivolumab and pembrolizumab. However, clinical benefit is only seen in roughly 15-20% of HNSCC patients treated with these agents. New molecular targeting agents are needed that either act with monotherapeutic activity against HNSCC tumors or enhance the activities of current therapies, particularly immunotherapy. Small-molecule tyrosine kinase inhibitors (TKIs) represent a viable option toward this goal.
This review provides an update on TKIs currently under investigation in HNSCC. We focus our review on data obtained and trials underway in HNSCC, including salivary gland cancers and nasopharyngeal carcinomas, but excluding thyroid cancer and esophageal cancer.
While some emerging TKIs have shown clinical benefit, the positive effects have, largely, been modest. The design of clinical trials of TKIs has been hampered by a lack of understanding of biomarkers that can be used to define patient populations most likely to respond. Further preclinical and translational studies to define biomarkers of TKI response will be critically important.
头颈部鳞状细胞癌（HNSCC）的传统治疗方案疗效有限，并伴有不良反应。食品和药物管理局（FDA）批准的分子靶向药物包括 HER1（EGFR）靶向单克隆抗体西妥昔单抗以及免疫检查点抑制剂纳武单抗和帕博利珠单抗。然而，这些药物治疗的 HNSCC 患者中，仅有约 15-20%观察到临床获益。需要新的分子靶向药物，这些药物要么具有针对 HNSCC 肿瘤的单药活性，要么增强现有疗法的活性，特别是免疫疗法。小分子酪氨酸激酶抑制剂（TKI）是实现这一目标的可行选择。
本综述介绍了目前在 HNSCC 中进行研究的 TKI。我们的综述重点关注在 HNSCC 中获得的数据和正在进行的试验，包括唾液腺癌和鼻咽癌，但不包括甲状腺癌和食管癌。
虽然一些新兴的 TKI 已显示出临床获益，但这些积极影响大多是适度的。TKI 临床试验的设计受到缺乏可用于定义最有可能应答的患者人群的生物标志物的阻碍。进一步的临床前和转化研究对于确定 TKI 反应的生物标志物将至关重要。
