Passiglia Francesco, Bironzo Paolo, Bertaglia Valentina, Listì Angela, Garbo Edoardo, Scagliotti Giorgio Vittorio
Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Italy.
Transl Lung Cancer Res. 2022 May;11(5):935-949. doi: 10.21037/tlcr-22-1.
Despite several steps forward in the treatment of epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC), however there are still pending issues and upcoming challenges requiring adequate addressing in order to optimize the clinical management of metastatic patients harboring molecular alterations within the gene. This review aims to summarize the most recent findings regarding the diagnostic testing and therapeutic strategies of -mutant advanced NSCLC.
Literature search was conducted using MEDLINE/PubMed, EMBASE, Scopus and Cochrane Library databases, up to December 2021. Relevant studies in English language published between 2004 and 2021 were selected.
The increased detection of uncommon mutations in the real-word practice along with the clinical development of novel selective inhibitors, highlighted the issue of an adequate selection of the best EGFR-tyrosine-kinase inhibitor (TKI) to the right patient mutation. The advent of osimertinib in first-line has dramatically changed the spectrum of molecular mechanisms underlying both innate and acquired resistance to the EGFR-TKI therapy, accelerating the clinical investigation of novel genomic-driven sequential strategies as well as upfront targeted combinations. The recent approval of potent, selective inhibitors targeting the exon-20 insertions, renewed interest toward this patients' subset, questioning the diagnostic accuracy of old-standard genomic sequencing technologies and pushing the implementations of next-generation sequencing (NGS)-based molecular profiling in the real word practice scenario.
This review provides evidence-based answers to the aforementioned challenges aiming to optimize the clinical management of metastatic patients harboring molecular alterations within the gene.
尽管表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）治疗已取得了一些进展，但仍存在待解决的问题和即将面临的挑战，需要加以妥善应对，以优化对携带EGFR基因分子改变的转移性患者的临床管理。本综述旨在总结关于EGFR突变的晚期NSCLC诊断检测和治疗策略的最新研究结果。
使用MEDLINE/PubMed、EMBASE、Scopus和Cochrane图书馆数据库进行文献检索，截至2021年12月。选取2004年至2021年期间发表的英文相关研究。
在实际临床实践中，罕见EGFR突变的检测增加，以及新型选择性抑制剂的临床研发，凸显了为合适的患者突变选择最佳EGFR酪氨酸激酶抑制剂（TKI）的问题。奥希替尼一线治疗的出现极大地改变了EGFR-TKI治疗原发和获得性耐药的分子机制谱，加速了新型基因组驱动序贯策略以及初始靶向联合治疗的临床研究。针对外显子20插入突变的强效、选择性抑制剂的近期获批，重新引发了对这一患者亚组的关注，质疑旧标准基因组测序技术的诊断准确性，并推动在实际临床场景中实施基于二代测序（NGS）的分子谱分析。
本综述为上述挑战提供了基于证据的答案，旨在优化对携带EGFR基因分子改变的转移性患者的临床管理。
