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

• Published in: BMC cancer 2021-11, Vol.21 (1), p.1215-1215, Article 1215
• Main Authors: Wang, Yurong, Zheng, Ruipan, Hu, Peizhu, Zhang, Ziheng, Shen, Shujing, Li, Xingya
• Format: Article
• Language: English
• Subjects: Acrylamides - therapeutic use; Adult; Aged; Aniline Compounds - therapeutic use; Biopsy; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Clinical outcomes; Disease Progression; Drug therapy; EGFR exon 19 deletion-insertion; EGFR TKI; Enzyme inhibitors; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; Exons; Female; Gene Deletion; Gene mutations; Genes, erbB-1; Genetic aspects; Genotype; Genotypes; Health aspects; Humans; Insertion; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Metastasis; Middle Aged; Mutagenesis, Insertional; Mutation; Next-generation sequencing; Non-small cell lung carcinoma; NSCLC; Patient outcomes; Patients; Pleural effusion; Progression-Free Survival; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Resistance mechanism; Retrospective Studies; Small cell lung carcinoma; Software; Survival analysis
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-08942-x

In 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. We 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. A 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). This 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.