Clinical Implications of the T790M Mutation in Disease Characteristics and Treatment Response in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Non–Small-Cell Lung Cancer (NSCLC)

Daria Gaut; Myung Shin Sim; Yuguang Yue; Brian R. Wolf; Phillip A. Abarca; James M. Carroll; Jonathan W. Goldman; Edward B. Garon

doi:10.1016/j.cllc.2017.06.004

Back

Clinical Implications of the T790M Mutation in Disease Characteristics and Treatment Response in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Non–Small-Cell Lung Cancer (NSCLC)

Journal article

Peer reviewed

Clinical Implications of the T790M Mutation in Disease Characteristics and Treatment Response in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Non–Small-Cell Lung Cancer (NSCLC)

Daria Gaut, Myung Shin Sim, Yuguang Yue, Brian R. Wolf, Phillip A. Abarca, James M. Carroll, Jonathan W. Goldman and Edward B. Garon

Clinical lung cancer, Vol.19(1), pp.e19-e28

01/2018

DOI: 10.1016/j.cllc.2017.06.004

PMCID: PMC5761337

PMID: 28712979

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/5761337View

Open Access

Abstract

We characterized differences in the natural history of patients with EGFR-mutated NSCLC whose tumors develop a T790M resistance mutation compared with those whose tumors do not. We found T790M+ patients had a longer PFS with first-line TKI and chemotherapy, but no difference with TKI rechallenge. Response rate was similar for all therapies evaluated, even when differences in PFS were seen. The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non–small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation–specific TKI. Medical records were retrospectively analyzed for demographic data, PFS, and best response to previous therapies. Our patient cohort included 69 T790M+ patients and 28 T790M− patients. Patients who later developed a T790M mutation had a longer PFS on first-line TKI therapy (12.0 vs. 9.0 months, P = .021), but overall response rate (ORR) was the same (75.0% vs. 81.0%, P = .76). There was no difference in PFS on TKI rechallenge (4.0 vs. 3.0 months, P = .94), although there was a trend toward higher ORR in T790M+ patients (22.2% vs. 0%, P = .12). T790M+ patients had a longer PFS on initial chemotherapy treatment (5.0 vs. 4.0 months, P = .025) and a trend toward higher ORR (40.0% vs. 21.4%, P = .31). Our study confirms that tumors expressing T790M have a more indolent progression of disease compared with their T790M− counterparts when treated with both first-line TKI and cytotoxic chemotherapy.

Acquired resistance

Chemotherapy

EGFR tyrosine kinase inhibitor

Progression-free survival

Targeted therapy

Details

Title: Subtitle: Clinical Implications of the T790M Mutation in Disease Characteristics and Treatment Response in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Non–Small-Cell Lung Cancer (NSCLC)
Creators: Daria Gaut - †Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Myung Shin Sim - University of California, Los Angeles
Yuguang Yue - University of California, Los Angeles
Brian R. Wolf - University of California, Los Angeles
Phillip A. Abarca - University of California, Los Angeles
James M. Carroll - University of California, Los Angeles
Jonathan W. Goldman - University of California, Los Angeles
Edward B. Garon - University of California, Los Angeles
Resource Type: Journal article
Publication Details: Clinical lung cancer, Vol.19(1), pp.e19-e28
DOI: 10.1016/j.cllc.2017.06.004
PMID: 28712979
PMCID: PMC5761337
NLM abbreviation: Clin Lung Cancer
ISSN: 1525-7304
eISSN: 1938-0690
Publisher: Elsevier Inc
Language: English
Date published: 01/2018
Academic Unit: Orthopedics and Rehabilitation; Physical Therapy and Rehabilitation Science
Record Identifier: 9984294955302771

Metrics

18 Record Views

20 Times Cited - Web of Science

See more details