INSERM U981, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, France.
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Nat Rev Clin Oncol. 2018 Nov;15(11):694-708. doi: 10.1038/s41571-018-0081-4.
The traditional approach to the treatment of patients with advanced-stage non-small-cell lung carcinoma (NSCLC) harbouring ALK rearrangements or EGFR mutations has been the sequential administration of therapies (sequential treatment approach), in which patients first receive first-generation tyrosine-kinase inhibitors (TKIs), which are eventually replaced by next-generation TKIs and/or chemotherapy upon disease progression, in a decision optionally guided by tumour molecular profiling. In the past few years, this strategy has been challenged by clinical evidence showing improved progression-free survival, improved intracranial disease control and a generally favourable toxicity profile when next-generation EGFR and ALK TKIs are used in the first-line setting. In this Review, we describe the existing preclinical and clinical evidence supporting both treatment strategies - the 'historical' sequential treatment strategy and the use of next-generation TKIs - as frontline therapies and discuss the suitability of both strategies for patients with EGFR-driven or ALK-driven NSCLC.
传统的治疗方法是对携带 ALK 重排或 EGFR 突变的晚期非小细胞肺癌 (NSCLC) 患者采用序贯治疗方法（sequential treatment approach），即患者首先接受第一代酪氨酸激酶抑制剂 (TKI)，在疾病进展时，根据肿瘤分子谱分析，可选择更换为第二代 TKI 和/或化疗。在过去的几年中，临床证据表明，当将下一代 EGFR 和 ALK TKI 用于一线治疗时，无进展生存期、颅内疾病控制和总体有利的毒性特征得到改善，这一策略受到了挑战。在这篇综述中，我们描述了支持这两种治疗策略（传统的序贯治疗策略和使用下一代 TKI）作为一线治疗的现有临床前和临床证据，并讨论了这两种策略对 EGFR 驱动或 ALK 驱动的 NSCLC 患者的适用性。
