Indiana University, Department of Medicine, Division of Hematology/Oncology, Melvin Bren and Simon Cancer Center, Indianapolis, IN.
Indiana University, Department of Medicine, Division of Hematology/Oncology, Melvin Bren and Simon Cancer Center, Indianapolis, IN.
Clin Lung Cancer. 2020 Jul;21(4):308-313. doi: 10.1016/j.cllc.2020.02.024. Epub 2020 Mar 12.
The treatment of advanced non-small-lung cancer (NSCLC) has steadily evolved over the past 2 decades, and current therapy includes chemoimmunotherapy or targeted therapy with tyrosine kinase inhibitors (TKIs). Angiogenesis inhibitors were first approved in the mid-2000s in combination with chemotherapy for the treatment of NSCLC. The addition of anti-angiogenics to chemotherapy resulted in modest increases in survival when median overall survival was less than 1 year. More recently, the use of anti-angiogenics has fallen out of favor with the advent of checkpoint inhibitors and never-before-seen durable long-term responses. However, we postulate that there is still an important role for anti-angiogenics in this era of targeted therapy and checkpoint inhibitors in the treatment of NSCLC. Preclinical studies have shown that combination blockade of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways leads to synergistic antitumor effects. These results have been replicated in the clinical setting in patients who harbor EGFR mutations, with VEGF inhibitor-TKI dual therapy leading to impressive survival outcomes. Similarly, combination treatment with checkpoint inhibitors and VEGF inhibitors have led to unprecedented survival outcomes in both advanced renal cell cancer as well as NSCLC. In this review, we explore the evolution of anti-angiogenic therapy in advanced NSCLC and discuss the clinical efficacy of angiogenesis inhibitors in combination with chemotherapy, TKI therapy, and checkpoint inhibitors.
在过去的 20 年中，晚期非小细胞肺癌（NSCLC）的治疗方法不断发展，目前的治疗方法包括化疗免疫治疗或酪氨酸激酶抑制剂（TKI）的靶向治疗。血管生成抑制剂于 21 世纪中期首次获准与化疗联合用于治疗 NSCLC。当中位总生存期不到 1 年时，抗血管生成药物与化疗联合使用可适度提高生存率。最近，随着检查点抑制剂的出现和前所未有的持久长期缓解，抗血管生成药物的使用已不再流行。然而，我们认为，在靶向治疗和检查点抑制剂治疗 NSCLC 的时代，抗血管生成药物仍然具有重要作用。临床前研究表明，联合阻断表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）途径可产生协同抗肿瘤作用。在携带 EGFR 突变的患者中，这些结果在临床环境中得到了复制，VEGF 抑制剂-TKI 双重治疗可带来令人印象深刻的生存结果。同样，检查点抑制剂和 VEGF 抑制剂联合治疗在晚期肾细胞癌和 NSCLC 中均带来了前所未有的生存结果。在这篇综述中，我们探讨了晚期 NSCLC 中抗血管生成治疗的演变，并讨论了血管生成抑制剂联合化疗、TKI 治疗和检查点抑制剂的临床疗效。
