Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.
Levine Cancer Institute, Charlotte, NC, United States of America.
Gynecol Oncol. 2023 Jul;174:148-156. doi: 10.1016/j.ygyno.2023.05.007. Epub 2023 May 17.
Oral tyrosine kinase inhibitors (TKIs) have new indications for treatment in gynecologic malignancies. These targeted drugs have both unique and overlapping toxicities, which require careful attention and management. New combination therapies with immune-oncology agents have demonstrated promise in endometrial cancer. This review examines common adverse events associated with TKIs and provides readers with an evidence-based review on current uses and strategies for the management of these medications.
A comprehensive review of the medical literature on TKI use in gynecologic cancer was undertaken by a committee approach. Details of each drug, its molecular target, and relevant data on both clinical efficacy and side effects were compiled and organized for clinical use. Information on drug-related secondary effects and management strategies for specific toxicities, including dose reduction and concomitant medications, were gathered.
TKIs can potentially offer improved response rates and durable responses for a group of patients who were previously without an effective standard second-line therapy. The combination of lenvatinib and pembrolizumab represents a more targeted approach to the drivers of endometrial cancer; however, there remains significant drug-related toxicity, and thus dose reduction and dose delay are frequently required. Toxicity management requires frequent check-ins and management strategies to help patients find the highest tolerable dose. TKIs are expensive and patient financial toxicity is as critical a measure of a drug's utility as any drug side effect. Many of these drugs have patient assistance programs, which should be fully utilized to minimize cost.
Future studies are needed to expand the role of TKIs into new molecularly driven groups. Attention to cost, durability of response, and long-term toxicity management is needed to ensure all eligible patients have access to treatment.
口服酪氨酸激酶抑制剂（TKI）在妇科恶性肿瘤治疗中有新的适应证。这些靶向药物具有独特和重叠的毒性，需要仔细注意和管理。免疫肿瘤药物的新联合疗法已在子宫内膜癌中显示出前景。本综述检查了与 TKI 相关的常见不良事件，并为读者提供了关于这些药物当前用途和管理策略的循证综述。
通过委员会方法对 TKI 在妇科癌症中的应用的医学文献进行了全面综述。详细说明了每种药物的分子靶点，以及关于临床疗效和副作用的相关数据，以便于临床使用。收集了有关药物相关的次要作用以及特定毒性的管理策略的信息，包括剂量减少和伴随药物。
TKI 有可能为一组以前没有有效标准二线治疗的患者提供更好的反应率和持久的反应。仑伐替尼和 pembrolizumab 的联合代表了针对子宫内膜癌驱动因素的更具针对性的方法；然而，仍然存在显著的药物相关毒性，因此经常需要减少剂量和延迟剂量。毒性管理需要频繁检查和管理策略，以帮助患者找到最高耐受剂量。TKI 昂贵，患者的财务毒性与任何药物副作用一样，是衡量药物效用的关键指标。许多这些药物都有患者援助计划，应充分利用这些计划来最大程度地降低成本。
需要进一步研究来扩大 TKI 在新的分子驱动群体中的作用。需要注意成本、反应的持久性和长期毒性管理，以确保所有符合条件的患者都能获得治疗。
