T790米
医学
表皮生长因子受体
肺癌
内科学
突变
肿瘤科
外显子
化疗
酪氨酸激酶抑制剂
癌症研究
酪氨酸激酶
病理
吉非替尼
癌症
受体
生物
基因
遗传学
作者
Varsha Singh,Aruna Nambirajan,Prabhat Singh Malik,Sanjay Thulkar,Ravindra Mohan Pandey,Kalpana Luthra,Sudheer Arava,Ruma Ray,Anant Mohan,Deepali Jain
出处
期刊:Lung Cancer
[Elsevier]
日期:2020-11-01
卷期号:149: 53-60
被引量:8
标识
DOI:10.1016/j.lungcan.2020.07.038
摘要
Mutations in the tyrosine kinase domain of the epidermal growth factor receptor gene (EGFR) are key driver alterations in lung adenocarcinomas (ADCAs). Exon 19 deletions (exon19del) and exon 21 L858R (L858R) mutations account for 70-90 % of all such alterations and predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). However, the predictive value of uncommon and compound EGFR mutations for TKIs has not been clearly established.To assess the spectrum of EGFR mutations in non-small-cell lung carcinoma (NSCLC), and to compare the treatment responses and outcomes among single common, single uncommon, and compound mutations.The study was of combined retrospective (January 2010-December 2015) and prospective (January 2016-February 2020) design spanning 10 years. Tumor samples from TKI-naive NSCLC patients were tested for EGFR mutations by a qPCR-based method. Objective response rates (ORRs) and survival outcomes were analyzed.In total, 1227 tumor samples were tested. EGFR mutations were detected in 391 samples (31.8 %), and included 79.5 % (311/391) single common (exon19del/L858R), 6.6 % (26/391) single uncommon (non-exon19del/L858R), and 13.8 % (54/391) compound mutations. Exon 20 T790M mutations were most prevalent among uncommon/compound mutations (40/391, 10.2 %). Overall, patients with single uncommon/compound mutations responded poorly to both EGFRTKI (47 % ORR) and chemotherapy (43 % ORR), with significantly shorter time to progression (median 7 months) compared to those with exon19del/L858R mutations (median 14.7 months). Patients with baseline T790M mutations (single/compound) were least responsive to EGFR TKIs (11 % ORR) and chemotherapy (27 % ORR) and showed the shortest progression-free survival compared to other uncommon and compound mutations.Approximately one fifth of EGFR-mutant patients harbor uncommon and compound mutations. Unlike those with exon19del/L858R, these patients-particularly those with baseline T790M mutations-show significantly inferior response rates to treatment (EGFR TKI or chemotherapy) and early disease progression.
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