A multicenter-retrospective study of non-small-cell lung carcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations: different subtypes of EGFR exon 19 deletion-insertions exhibit the clinical characteristics and prognosis of non-small cell lung carcinoma

Background: The aim of this study was to investigate the clinical features, immunohistochemistry (IHC), compound mutation, and prognosis of patients with non-small cell lung cancer (NSCLC) harboring exon 19 deletion-insertion mutations. Methods: This retrospective analysis included 4,666 NSCLC patients harboring EGFR mutations in a multi-center study from January 2017 to December 2020, and 69 patients with EGFR exon 19 deletion-insertions were taken to account. Next-generation sequencing (NGS) was used to detect the subtype of EGFR exon 19 deletion-insertions. These mutations were correlated with clinical features, immunophenotype and molecular characteristics of tumors and outcomes of patients. Results: Sixty-nine patients with EGFR exon 19 deletion-insertions were analyzed in this study, comprising 24 cases (34.8%) with L747_P753delinsS, 9 cases (13.1%) with L747_A750delinsP, both 5 cases (7.2%) in E746_A750delinsQP, E746_S752delinsV and both 4 cases (5.8% ) in E746_T751delinsA and L747_ T751delinsP. Twenty-nine males (42%) and 40 females (58%), with a median age of 59.7 years; 12 (21.7%) participants were smokers and 54 (78.3%) were nonsmokers. The compound mutations were tumor protein 53 (TP53) (45.83%), phosphoinositide-3-kinase (PIK3CA) (11.59%), and almost 16.67% in retinoblastoma 1 (RB1), melanocyte stimulating hormone (MSH), and myelocytomatosis (MYC). The best overall response was complete response (CR) in 47.8% of patients, partial response (PR) in 33.3% and stable disease (SD) in 13.1% of patients. Correlation between immunoreactivity of Napsin A, thyroid transcription factor (TTF), cytokeratin (CK7), surfactant proteins B (SPB), and the subtypes of EGFR exon 19 deletion-insertion was significantly statistically different (P<0.05). The disease control rate (DCR) was 29%. The median progression-free survival (mPFS) and 95% confidence interval (CI) of exon 19 deletion-insertion subtypes were 14.821 (9.917 to 19.726) months for L747_P753delinsS, 23.500 (15.877 to 31.123) months for L747_ A750delinsP, 26.667 (11.731 to 41.603) months for L747_T751delinsP, and 11.713 (7.786 to 15.639) months for the others. Patients receiving treatment with 3rd generation tyrosine kinase inhibitors (TKI) had the shortest PFS (median: 7.179, 95% CI: 3.969-10.388). Conclusions: The subtypes of exon 19 deletion-insertion exhibited different clinical characteristics compared with other common mutations. Our finding argued in favor of analyzing the correlation between immunoreactivity and the subtypes of EGFR exon 19 deletion-insertion. The EGFR exon 19 deletion insertion mutations exhibited limited sensitivity to 3rd generation TKI. Moreover, in light of therapeutic effect for the subtype, L747_T751delinsP achieved longer PFS.