Chelabi Samy, Mignard Xavier, Leroy Karen, Monnet Isabelle, Brosseau Solenn, Theou-Anton Nathalie, Massiani Marie-Ange, Friard Sylvie, Duchemann Boris, Fabre Elizabeth, Giroux-Leprieur Etienne, Cadranel Jacques, Wislez Marie
Oncology Thoracic Unit, Pulmonology Department, AP-HP, Hôpital Cochin, F-75014 Paris, France.
Biochemistry Department, AP-HP, Hôpital Européen Georges Pompidou, F-75015 Paris, France.
Cancers (Basel). 2021 Oct 13;13(20):5132. doi: 10.3390/cancers13205132.
EGFR exon 20 insertions are rare genetic alterations in non-small-cell lung cancers (NSCLCs) that are usually unresponsive to approved EGFR tyrosine kinase inhibitors (TKIs). In this paper, we describe the clinical characteristics, efficacy of EFGR TKIs and chemotherapy, and resulting survival in this population. We retrospectively collected patients with EGFR exon 20 insertions (Exon20ins) from 11 French genetic platforms and paired them (1:2 ratio) with classic Exon 19/21 EGFR mutation patients (controls). Between 2012 and 2017, 35 Exon20ins patients were included. These patients were younger at diagnosis than the controls. All Exon20ins patients who were treated with first-line EGFR TKIs ( = 6) showed progressive disease as the best tumor response. There was no significant difference in the tumor response or the disease control rate with first-line platinum-based chemotherapy between the two groups. A trend towards shorter overall survival was observed in Exon20ins vs. controls (17 months (14-not reach(NR) 95% confidence interval(CI) vs. 29 months (17-NR 95%CI), = 0.09), respectively. A significant heterogeneity in amino acid insertion in EGFR exon 20 was observed. EGFR exon 20 insertions are heterogeneous molecular alterations in NSCLC that are resistant to classic EGFR TKIs, which contraindicates their use as a first-line treatment.
表皮生长因子受体（EGFR）第20外显子插入是一种在非小细胞肺癌（NSCLC）中罕见的基因改变，通常对已获批的EGFR酪氨酸激酶抑制剂（TKIs）无反应。在本文中，我们描述了该人群的临床特征、EGFR TKIs和化疗的疗效以及由此产生的生存率。我们从11个法国基因平台回顾性收集了EGFR第20外显子插入（Exon20ins）患者，并将他们（1:2的比例）与经典的第19/21外显子EGFR突变患者（对照组）进行配对。在2012年至2017年期间，纳入了35例Exon20ins患者。这些患者诊断时比对照组年轻。所有接受一线EGFR TKIs治疗的Exon20ins患者（n = 6）均显示疾病进展为最佳肿瘤反应。两组之间一线铂类化疗的肿瘤反应或疾病控制率无显著差异。Exon20ins患者与对照组相比，总生存期有缩短的趋势（分别为17个月（14-未达到（NR）95%置信区间（CI））和29个月（17-NR 95%CI），P = 0.09）。观察到EGFR第20外显子氨基酸插入存在显著异质性。EGFR第20外显子插入是NSCLC中对经典EGFR TKIs耐药的异质性分子改变，这表明它们不适合用作一线治疗。
