Primary and acquired EGFR T790M-mutant NSCLC patients identified by routine mutation testing show different characteristics but may both respond to osimertinib treatment.

Abstract

Primary EGFR T790M mutation is occasionally identified by routine mutation testing in tyrosine kinase inhibitor (TKI)-naive patients with non-small cell lung cancer (NSCLC). We herein aimed to compare the characteristics of primary and acquired T790M mutations in NSCLC patients, and their response to osimertinib. Using amplification refractory mutation system (ARMS) detection, primary T790M was identified in 0.5% (46/8723) of TKI-naive patients, whereas acquired T790M was detected in 49.7% (71/143) of TKI-relapsed patients. T790M always coexisted with a sensitizing EGFR mutation. Primary T790M more commonly coexisted with L858R, whereas acquired T790M was more likely to coexist with exon 19 deletions. Moreover, next-generation sequencing (NGS) showed that concomitant sensitizing EGFR and primary T790M mutant allele frequencies (MAFs) were highly concordant, but acquired T790M MAFs were significantly lower than the sensitizing EGFR MAFs. Sixteen acquired T790M-mutant patients received osimertinib. The median progression-free survival (PFS) was 8.1 months. Four primary T790M-mutant patients received osimertinib and the median PFS was 8.0 months. Together, our study demonstrates that primary and acquired T790M-mutant patients show distinct differences in some clinical and molecular characteristics, but may both respond to osimertinib treatment.

• Authors: Weihua Li, Tian Qiu, Lei Guo, Yun Ling, Yibo Gao, Jianming Ying, Jie He
• Journal: Cancer letters (Cancer Lett) Vol. 423 Pg. 9-15 (06 01 2018) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 29524556 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Acrylamides
• Aniline Compounds
• Piperazines
• Protein Kinase Inhibitors
• osimertinib
• EGFR protein, human
• ErbB Receptors

Topics

• Acrylamides
• Adult
• Aged
• Aged, 80 and over
• Aniline Compounds
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Diagnostic Tests, Routine
• Drug Resistance, Neoplasm
• ErbB Receptors (genetics)
• Female
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Male
• Middle Aged
• Mutation
• Piperazines (administration & dosage, therapeutic use)
• Progression-Free Survival
• Protein Kinase Inhibitors (administration & dosage, therapeutic use)
• Retrospective Studies
• Sequence Analysis, DNA
• Treatment Outcome
• Young Adult