Department of Hematology and Oncology, University Dept Internal Medicine-Oncology, Pius-Hospital, Medical Campus University of Oldenburg, Oldenburg, Germany.
Curr Opin Oncol. 2019 Jan;31(1):1-7. doi: 10.1097/CCO.0000000000000495.
Epidermal growth factor receptor (EGFR) mt+ nonsmall cell lung cancer (NSCLC) were the first molecularly described NSCLC with an established 'targeted' therapy inhibiting mutated EGFR [EGFR tyrosine kinase inhibitor (TKI)]. EGFR TKI of first and second generation have led to an unprecedented improvement in objective response rate, progression-free survival (PFS) and overall survival (OS) compared with chemotherapy with a significantly reduced toxicity and improved quality of life. Fast elucidation of the most frequent resistance mechanism against first and second-generation TKI, T790M, led to the approval of the third-generation TKI osimertinib in second line.
Recently, the FLAURA study showed an impressive PFS benefit and immature OS data for osimertinib against solely first-generation TKI's. Also, the ARCHER study comparing dacomitinib against first-generation TKI showed a PFS and also OS benefit. Two studies combining EGFR TKI and antiangiogenesis showed PFS but no OS benefit. Lately, the combination of TKI and chemotherapy has seen a revival with the NEJ009 study, resulting in an impressive median OS of 55 months.
Therefore, potentially four different therapeutic options are available in first-line therapy of EGFR mt+ NSCLC, first, second, third generation, TKI + antiangiogenic agent and TKI + chemotherapy. The purpose of the review is to help to guide physicians to decide in their treatment choice and discuss potential directions of research.
表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）是首个分子描述明确的 NSCLC，存在既定的“靶向”治疗方法，即抑制突变的 EGFR [EGFR 酪氨酸激酶抑制剂（TKI）]。与化疗相比，第一代和第二代 EGFR TKI 显著提高了客观缓解率、无进展生存期（PFS）和总生存期（OS），同时毒性降低，生活质量提高。快速阐明针对第一代和第二代 TKI 的最常见耐药机制 T790M，导致第三代 TKI 奥希替尼在二线获批。
最近，FLAURA 研究显示，奥希替尼对比单纯第一代 TKI 可显著改善 PFS，OS 数据不成熟。此外，ARCHER 研究比较达克替尼与第一代 TKI，显示出 PFS 和 OS 获益。两项联合 EGFR TKI 和抗血管生成药物的研究显示出 PFS 获益，但 OS 无获益。最近，TKI 联合化疗的治疗方案在 NEJ009 研究中重新得到应用，中位 OS 达到了 55 个月。
因此，在 EGFR mt+ NSCLC 的一线治疗中，有四种不同的治疗选择，分别是第一代、第二代、第三代、TKI+抗血管生成药物和 TKI+化疗。本文综述的目的是帮助指导医生在治疗选择中做出决策，并讨论潜在的研究方向。
