The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Abstract

PurposeThe main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)‒mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR‒tyrosine kinase inhibitor (TKI) treatment.Materials and MethodsWe enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status.ResultsA total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032).ConclusionPFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.

Association between programmed death-ligand 1 expression, immune microenvironments, and clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients treated with tyrosine kinase inhibitors

“…If clinical application is considered, predicting the emergence of T790M resistance before EGFR TKI treatment is more important and may provide help in tailoring further therapies while the tumour progresses, especially when re-biopsy or liquid biopsy is not feasible. Huang et al reported that longer PFS of first-line TKI and baseline exon 19 deletions were associated with higher frequency acquired T790M mutation [39]. In our analyses, we found that low PD-L1 expression (PD-L1 TPS 0% versus 1e100%) was an independent factor associated with the T790M mutation, after adjusting PFS as a factor.…”

Clinical outcomes and secondary epidermal growth factor receptor (EGFR) T790M mutation among first‐line gefitinib, erlotinib and afatinib‐treated non‐small cell lung cancer patients with activating EGFR mutations

“…Huang et al . also found that PFS of more than 11 months was associated with secondary EGFR T790M mutation with an AUC of 0.594 . Since post‐progression use of EGFR TKI is not uncommon, we thought EGFR TKI duration may be more appropriate than EGFR TKI PFS for TKI exposure.…”

“…and Huang et al . also reported that those with an EGFR exon 19 deletion were more likely to develop secondary T790M than those with EGFR L858R, as well as uncommon mutations in cohorts with a majority of patients (96% and 94%, respectively) treated with gefitinib or erlotinib . A prior study by Wu et al .…”

“…46 Huang et al also found that PFS of more than 11 months was associated with secondary EGFR T790M mutation with an AUC of 0.594. 47 Since post-progression use of EGFR TKI is not uncommon, we thought EGFR TKI duration may be more appropriate than EGFR TKI PFS for TKI exposure. Longer EGFR TKI duration may also imply that the cancer continually depends on the EGFR pathway, rather than other bypass pathways, and thus develops a secondary EGFR T790M mutation to maintain the EGFR pathway for tumor survival and proliferation.…”

Clinical Features and Progression Pattern of Acquired T790M-positive Compared With T790M-negative EGFR Mutant Non–small-cell Lung Cancer: Catching Tumor and Clinical Heterogeneity Over Time Through Liquid Biopsy

“…To date, mostly retrospective [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] and 2 prospective 46,47 Asian case series investigated clinical-pathologic characteristics of T790M mutant lung cancer. Only a few data are available in Caucasian patients, and none of these studies investigated clinical progression patterns related to T790M in detail.…”