Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib

A Oztan; S Fischer; A B Schrock; R L Erlich; C M Lovly; P J Stephens; J S Ross; V Miller; S M Ali; S-H I Ou; L E Raez

doi:10.1016/j.lungcan.2017.07.002

Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib

Lung Cancer. 2017 Sep:111:84-87. doi: 10.1016/j.lungcan.2017.07.002. Epub 2017 Jul 8.

Authors

A Oztan¹, S Fischer², A B Schrock³, R L Erlich³, C M Lovly⁴, P J Stephens³, J S Ross³, V Miller³, S M Ali³, S-H I Ou⁵, L E Raez⁶

Affiliations

¹ Foundation Medicine, Inc., 150 Second Street, Cambridge, MA 02141, USA. Electronic address: amatos@foundationmedicine.com.
² Providence Medical Institute, 2021 Santa Monica Blvd, Santa Monica, CA 90404, USA.
³ Foundation Medicine, Inc., 150 Second Street, Cambridge, MA 02141, USA.
⁴ Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA.
⁵ Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA 92868, USA.
⁶ Memorial Cancer Institute/Memorial Healthcare System, 801 N. Flamingo Road, Pembroke Pines, FL 33028, USA.

PMID: 28838405
DOI: 10.1016/j.lungcan.2017.07.002

Abstract

Mutations in the epidermal growth factor receptor (EGFR) are drivers for a subset of lung cancers. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) recently approved for the treatment of T790M-positive non-small cell lung cancer (NSCLC); however, acquired resistance to osimertinib is evident and resistance mechanisms remain incompletely defined. The EGFR G724S mutation was detected using hybrid-capture based comprehensive genomic profiling (CGP) and a hybrid-capture based circulating tumor DNA (ctDNA) assays in two cases of EGFR-driven lung adenocarcinoma in patients who had progressed on osimertinib treatment. This study demonstrates the importance of both tissue and blood based hybrid-capture based genomic profiling at disease progression to identifying novel resistance mechanisms in the clinic.

Keywords: Acquired resistance; EGFR; G724S; Lung cancer; Osimertinib; T790M.

Publication types

Case Reports

MeSH terms

Acrylamides
Adenocarcinoma / drug therapy
Adenocarcinoma / genetics*
Adenocarcinoma / pathology*
Adenocarcinoma of Lung
Aged
Alleles*
Amino Acid Substitution*
Aniline Compounds
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Disease Progression
Drug Resistance, Neoplasm / genetics
ErbB Receptors / genetics*
Exons
Fatal Outcome
Female
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / pathology*
Male
Middle Aged
Mutation*
Neoplasm Staging
Piperazines / pharmacology
Piperazines / therapeutic use
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Tomography, X-Ray Computed
Treatment Outcome

Substances

Acrylamides
Aniline Compounds
Antineoplastic Agents
Piperazines
Protein Kinase Inhibitors
osimertinib
ErbB Receptors