Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Lilly China Drug Development and Medical Affairs Center, Shanghai, People's Republic of China.
J Thorac Oncol. 2016 Feb;11(2):174-86. doi: 10.1016/j.jtho.2015.10.002. Epub 2015 Dec 19.
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) monotherapy has been regarded as the standard first-line treatment of advanced non-small cell lung cancer (NSCLC) in patients with sensitive epidermal growth factor receptor gene (EGFR) mutations. Acquired resistance is inevitable, however, which presents a challenge in the management of patients with such mutations. Here, we summarize the clinical evidence on treatment strategies for both EGFR TKI-naive and acquired EGFR TKI-resistant NSCLC. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing treatment strategies that are in use or in clinical development to improve the survival of patients who are EGFR TKI naive and EGFR TKI resistant. Various strategies have been explored to manage EGFR TKI resistance with the aim of prolonging the survival of patients with EGFR-mutant NSCLC. Combination strategies in the first-line treatment have been studied most to improve the benefit from EGFR TKI monotherapy and delay the occurrence of resistance. After failure of EGFR TKI monotherapy, continuation of EGFR TKI therapy combined with chemotherapy, immunotherapy, or targeted agents has been used to overcome the development of resistance. In addition, novel compounds designed to act on specific targets associated with EGFR TKI resistance have been in continued clinical development. Treatment regimens that are superior to EGFR TKI monotherapy in the first-line or to overcome acquired EGFR TKI resistance in patients with NSCLC and EGFR mutations still need to be developed. Results of ongoing studies will provide more insight into effective treatment strategies for patients with EGFR mutations.
表皮生长因子受体酪氨酸激酶抑制剂(EGFR TKI)单药治疗已被视为具有敏感表皮生长因子受体基因(EGFR)突变的晚期非小细胞肺癌(NSCLC)患者的标准一线治疗。然而,获得性耐药是不可避免的,这给此类突变患者的管理带来了挑战。在这里,我们总结了 EGFR TKI 初治和获得性 EGFR TKI 耐药 NSCLC 的治疗策略的临床证据。我们回顾了已发表的文献和国际会议的口头和海报摘要,这些文献和摘要涉及目前正在使用或正在临床开发中的治疗策略,以改善 EGFR TKI 初治和 EGFR TKI 耐药的患者的生存。已经探索了各种策略来管理 EGFR TKI 耐药,旨在延长 EGFR 突变型 NSCLC 患者的生存。在一线治疗中已经研究了联合策略,以提高 EGFR TKI 单药治疗的获益并延迟耐药的发生。在 EGFR TKI 单药治疗失败后,继续使用 EGFR TKI 联合化疗、免疫治疗或靶向药物治疗已被用于克服耐药的发生。此外,设计用于针对与 EGFR TKI 耐药相关的特定靶点的新型化合物也在持续临床开发中。需要开发出在一线治疗中优于 EGFR TKI 单药治疗或克服 EGFR 突变 NSCLC 患者获得性 EGFR TKI 耐药的治疗方案。正在进行的研究结果将为 EGFR 突变患者提供更有效的治疗策略。