Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M

BMC Cancer

Yurong Wang¹  Xingya Li¹  Ziheng Zhang¹  Peizhu Hu²  Shujing Shen³  Ruipan Zheng³ 

[1] Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road 1, 450052, Zhengzhou, Henan, People’s Republic of China;Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road 1, 450052, Zhengzhou, Henan, People’s Republic of China;Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road 1, 450052, Zhengzhou, Henan, People’s Republic of China;

关键词: EGFR exon 19 deletion-insertion;    EGFR TKI;    Clinical outcomes;    Resistance mechanism;    NSCLC;   

DOI  :  10.1186/s12885-021-08942-x

来源: Springer

【 摘 要 】

BackgroundIn the existing next generation sequencing (NGS) system, epidermal growth factor receptor (EGFR) exon 19 deletion-insertion (19delins) is still interpreted into the category of EGFR exon 19 deletion (19del). However, the controversy exists whether the two mutation types have the similar responses and resistant mechanisms to first-generation EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients.MethodsWe successively and retrospectively reviewed the NGS data of 3054 patients diagnosed as advanced NSCLC from November 2017 to September 2020. Finally, 41 patients with EGFR 19delins mutation and 41 patients with EGFR 19del mutation who received first-generation EGFR TKIs as first-line therapy were included in the study.ResultsA total of 17 genotypes were identified in this study, including L747_P753delinsS (10/41), L747_A750delinsP (9/41), L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, the population of EGFR 19delins respond well to first line EGFR TKIs as well as those of EGFR 19del, with little difference in median progression-free survival (mPFS): 10.4 months vs. 13.1 months, p = 0.1076). Interestingly, patients with L747_T751delinsP seem to have a better mPFS than others (18.7 months vs. 13.1 months, p = 0.035). After the disease progression, both EGFR 19delins and EGFR 19del had similar rates of developing EGFR T790M mutation resistance (45.8% vs. 57.8%), and those receiving osimeritinib as second-line treatment obtain the similar survival benefits (mPFS: 12.0 months vs. 12.2 months (p = 0.97).ConclusionsThis retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.

【 授权许可】

CC BY