Clinical outcomes of EGFR kinase domain duplication to targeted therapies in NSCLC.
Authors of this article are:
Wang J Li X Xue X Ou Q Wu X Liang Y Wang X You M Shao YW Zhang Z Zhang S.
A summary of the article is shown below:
Kinase domain duplications of the epidermal growth factor receptor (EGFR-KDD) have been identified and implicated to be oncogenic in non-small cell lung cancers (NSCLCs). However, its prevalence and clinical contributions in lung cancer are largely unknown. Here, we conducted a multi-center record review of 10,759 NSCLC patients who underwent genetic testing using next-generation sequencing (NGS) targeting EGFR exons and the introns involved in EGFR-KDD rearrangements. EGFR-KDDs were identified in a total of 13 patients, which is approximately 0.12% of the total population reviewed, and also consisted of 0.24% (13/5394) of EGFR mutation-positive patients. A total of 85% of patients (11/13) were identified with the canonical EGFR-KDD duplication of exons 18-25, while the remaining two cases harbored duplications of EGFR exons 14-26 and exons 17-25, which have not been previously described. Importantly, none of the 13 patients had other co-existing driver mutations, highlighting the potential oncogenic role of this type of alteration. Three out of five patients who had exon 18-25 duplications showed partial anti-tumor responses to targeted therapies, while the other two patients demonstrated no clinical improvement. Furthermore, our data suggested that the EGFR T790M mutation and EGFR amplification may represent the major resistance mechanisms against targeted therapies in tumors bearing EGFR-KDD. In summary, our findings provide valuable insight into the prevalence of EGFR-KDDs in NSCLCs and their clinical outcomes to targeted therapies. This article is protected by copyright. All rights reserved.
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