UW Health, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital Madison, WI, USA.
J Oncol Pharm Pract. 2021 Jun;27(4):930-938. doi: 10.1177/1078155220984235. Epub 2021 Jan 6.
The purpose of this review was to summarize the triumphs and pitfalls of tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) combinations. A literature review of PubMed was conducted and studies were included if they were classified as a clinical trial and assessed TKI and ICI combinations for solid tumor malignancies. Dates of literature search included January 1, 1988 through September 22, 2019. In the past decade, TKI and ICI monotherapy strategies have changed the management of many advanced solid tumors through their unique mechanisms of action. Preclinical data suggests that TKIs may be able to sensitize tumors to ICI therapy via direct and indirect pathways; however, optimal mechanisms to support various TKI and ICI combinations have yet to be determined. The FDA recently approved TKI and ICI combinations for renal cell carcinoma, endometrial carcinoma, and melanoma. Several other tumor types currently have TKI and immunotherapy combinations under investigation with mixed results. Dual therapy with TKIs and immunotherapy have the potential to be synergistic and improve patient outcomes; however, careful consideration will need to be taken in regard to what TKI and immunotherapy are combined.
Future research will be needed to determine appropriate sequencing of TKIs and ICIs after progression on combination therapy. Continued research is necessary to determine optimal dual TKI and immunotherapy options.
本文综述了酪氨酸激酶抑制剂（TKI）和免疫检查点抑制剂（ICI）联合治疗的成功与失败。对 PubMed 进行了文献回顾，纳入了评估 TKI 和 ICI 联合治疗实体瘤恶性肿瘤的临床试验。文献检索日期为 1988 年 1 月 1 日至 2019 年 9 月 22 日。在过去的十年中，TKI 和 ICI 的单药治疗策略通过其独特的作用机制改变了许多晚期实体瘤的治疗管理。临床前数据表明，TKI 可能通过直接和间接途径使肿瘤对 ICI 治疗敏感；然而，支持各种 TKI 和 ICI 联合治疗的最佳机制仍有待确定。美国食品和药物管理局（FDA）最近批准了 TKI 和 ICI 联合治疗肾细胞癌、子宫内膜癌和黑色素瘤。目前，其他几种肿瘤类型也正在研究 TKI 和免疫治疗联合治疗，结果喜忧参半。TKI 和免疫治疗的双重治疗具有协同作用并改善患者预后的潜力；然而，需要仔细考虑联合治疗中使用哪些 TKI 和免疫治疗药物。
需要进一步的研究来确定在联合治疗进展后 TKI 和 ICI 的适当序贯治疗。需要进一步的研究来确定最佳的双重 TKI 和免疫治疗方案。
