The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M

Abstract

Different growth kinetics occurring between the sensitive and T790M-containing cells may result in the repopulation of tumor cells over time. Little information has yet been uncovered on whether rebiopsy timing influences the T790M detection rate. We enrolled a total of 98 epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients, who had a history of acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) and available rebiopsy tumor specimens for reassessment of EGFR mutations. Rebiopsy was performed at the time of first EGFR-TKI progression in 54 patients (55.1%); for the other 44 patients (44.9%), rebiopsy was done with an interval from first EGFR-TKI progression (median 470.5 days, range 46-1742 days). Our results indicated that rebiopsy timing did not influence the detection rate of T790M and that the mutation could be identified in patients with a long EGFR-TKI-free interval. For patients without suitable lesions for rebiopsy at the time of EGFR-TKI progression, an attempt to rebiopsy should be considered during the subsequent treatment courses.

Feasibility of re‐biopsy and EGFR mutation analysis in patients with non‐small cell lung cancer

“…The complication rate was 8.6% and mortality was 0.95%. T790M mutations were reported in 33.3% of cases, unlike previous reports that detected such mutations in approximately 50% of patients . We were unable to determine the specific characteristics related to T790M prevalence.…”

“…T790M mutations are the most common acquired resistance mechanism, accounting for 50% to 63% of mutations . In this study, using the PNA Clamp method, only 33.9% of patients with sensitizing mutations exhibited T790M mutations.…”

“…T790M mutations were reported in 33.3% of cases, unlike previous reports that detected such mutations in approximately 50% of patients. 7,10,[16][17][18] We were unable to determine the specific characteristics related to T790M prevalence. With the development of new treatments for NSCLC, including third-generation EGFR-TKIs and immune checkpoint inhibitors, the importance of re-biopsy has increased.…”

Characteristics of progression to tyrosine kinase inhibitors predict overall survival in patients with advanced non-small cell lung cancer harboring an EGFR mutation

“…This could be explained because a longer exposure to a TKI confers the time to develop a resistance mutation. Following this observation, previous studies have shown slower cell growth and favorable outcomes in patients with acquired resistance to EGFR-TKI associated to T790M mutations (32)(33)(34)(35).…”

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.…”