常见的 EGFR 基因突变（外显子 19 缺失和外显子 21 中的 L858R）是非小细胞肺癌 (NSCLC) 患者中可操作的基因组改变的最常见原因。 EGFR 酪氨酸激酶抑制剂 (TKI) 作为晚期疾病的一线治疗的引入改变了疾病的自然史并延长了生存率，确立了第三代 TKI 作为一线治疗的新标准。尽管如此，总生存期的延长仍然有限，因为随着时间的推移，多种逃逸途径和肿瘤异质性不可避免地会增加。目前开发了几种策略来改善这些患者的结果：通过从一线引入的治疗组合来预防耐药机制的出现，在对一线治疗产生最大反应时作用于残留疾病，在一线治疗出现最大反应时制定治疗策略对 TKI 的获得性耐药，要么取决于耐药机制，要么与耐药途径无关。治疗组合的最新进展在延长无进展生存期方面显示出有希望的结果，但与目前的护理标准相比，往往会产生更严重的副作用。这些新兴的治疗方案为根据常见 EGFR 突变治疗晚期 NSCLC 的多种治疗序列开辟了可能性。对疾病自然史、患者生存和生活质量的影响尚未完全了解。在这篇综述中，我们提出了对已发表和即将到来的进展的概述，以及考虑不同一线选项的管理算法，整合了对临床医生决策过程至关重要的临床和生物学参数。版权所有 © 2024 ）。由 Elsevier B.V. 出版。保留所有权利。

Common EGFR gene mutations (exon 19 deletion and L858R in exon 21) are the most frequent cause of actionable genomic alterations in non-small cell lung cancer (NSCLC) patients. The introduction of EGFR tyrosine kinase inhibitors (TKIs) as 1st-line treatment of advanced stages of the disease has changed the natural history of the disease and extended survival rates, establishing third generation TKIs as a new standard of frontline treatment. Nonetheless, the prolongation of overall survival remains modest, as multiple escape pathways and tumor increasing heterogeneity inevitably develop over time. Several strategies are currently developed to improve these patients' outcome: prevent the emergence of resistance mechanisms by therapeutic combinations introduced from the first line, act on the residual disease at the time of maximum response to 1st line treatment, develop therapeutic strategies at the time of acquired resistance to TKIs, either dependent on the resistance mechanisms, or agnostic of the resistance pathways. Recent advancements in treatment combinations have shown promising results in prolonging progression-free survival, but often at the cost of more severe side effects in comparison with the current standard of care. These emerging new treatment options open up possibilities for diverse therapeutic sequences in the management of advanced NSCLC depending on common EGFR mutations. The impact on the disease natural history, the patients' survival and quality of life is not yet fully understood. In this review, we propose an overview of published and forthcoming advances, and a management algorithm considering the different first-line options, integrating the clinical and biological parameters that are critical to clinicians' decision-making process.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.