Non-classic EGFR mutations in a cohort of Dutch EGFR-mutated NSCLC patients and outcomes following EGFR-TKI treatment

Abstract

Background:Data on non-small-cell lung cancer (NSCLC) patients with non-classic epidermal growth factor receptor (EGFR) mutations are scarce, especially in non-Asian populations. The purpose of this study was to evaluate prevalence, clinical characteristics and outcome on EGFR-TKI treatment according to type of EGFR mutation in a Dutch cohort of NSCLC patients.Methods:We retrospectively evaluated a cohort of 240 EGFR-mutated NSCLC patients. Data on demographics, clinical and tumour-related features, EGFR-TKI treatment and clinical outcome were collected and compared between patients with classic EGFR mutations, EGFR exon 20 insertions and other uncommon EGFR mutations.Results:Classic EGFR mutations were detected in 186 patients (77.5%) and non-classic EGFR mutations in 54 patients (22.5%); 23 patients with an exon 20 insertion (9.6%) and 31 patients with an uncommon EGFR mutation (12.9%). Median progression-free survival (PFS) and overall survival (OS) on EGFR-TKI treatment were 2.9 and 9.7 months, respectively, for patients with an EGFR exon 20 insertion, and 6.4 and 20.2 months, respectively, for patients with an uncommon EGFR mutation. Patients with a double uncommon EGFR mutation that included G719X/L861Q/S768I had longer PFS and OS on EGFR-TKI treatment compared with patients with a single G719X/L861Q/S768I EGFR mutation (both P=0.02).Conclusions:In our Dutch cohort, prevalence and genotype distribution of non-classic EGFR mutations were in accordance with previously reported data. The PFS and OS on EGFR-TKI treatment in patients with an uncommon EGFR mutation were shorter compared with patients with classic EGFR mutations, but varied among different uncommon EGFR mutations.

Uncommon <em>EGFR</em> mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

“…These common mutations generally comprised 80%–90% of total EGFR mutations, while the remaining mutations or uncommon mutations contributed 10%–20%. 26 , 27 However, our population had high rates of uncommon mutations (composed of G719X, exon 20 insertions, T790M, and L861Q) contributing up to 43% of total EGFR mutations. High proportion of uncommon EGFR mutations to total EGFR mutations has been reported in European population (50%) 28 and Chinese regions of Yunnan Province (70%).…”

Oncogenic driver mutations, treatment, and EGFR-TKI resistance in a Caucasian population with non-small cell lung cancer: survival in clinical practice

“…In line with previous reports, EGFR -positive patients with exon 19 mutations had a trend to longer OS (39 months) than those with an exon 21 mutation (34 months) [ 5 , 20 ]. The five patients with rare exon 18 mutations showed an even better survival, but due to small numbers, no final conclusions can be drawn [ 59 ]. Time on TKI-treatment included a median of 14 months on TKI beyond progression which prolongs disease control [ 60 ] and may, by preventing early switch to chemotherapy, positively influence patients’ quality of life [ 31 ].…”

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

“…12,13 Despite being excluded from most clinical trials, 7% to 23% of NSCLC tumors harbor uncommon EGFR mutations. [14][15][16][17][18][19][20][21] These mutations represent a highly heterogeneous group with almost 600 variants identified. 22 The most prevalent categories include exon 20 insertions (w6% of all EGFR mutations), G719X (w3%), L861Q (w1%), S768I (w1%), and exon 19 insertions (0.6%).…”