Format

Send to

Choose Destination
Clin Cancer Res. 2016 Mar 1;22(5):1103-10. doi: 10.1158/1078-0432.CCR-15-1031. Epub 2015 Oct 7.

Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses.

Author information

1
Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Department of Medicine, Harvard Medical School, Boston, Massachusetts.
2
Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Medicine, Thoracic Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York.
4
Department of Medicine, Harvard Medical School, Boston, Massachusetts. Lowe Center for Thoracic Oncology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
5
Roche Molecular Systems, Inc., Pleasanton, California.
6
MGH Biostatistics Center, Boston, Massachusetts.
7
EKF Molecular Diagnostics, Ltd., Cardiff, United Kingdom.
8
Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York.
9
BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
10
Department of Medicine, Harvard Medical School, Boston, Massachusetts. BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
11
Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Department of Surgery, Harvard Medical School, Boston, Massachusetts.
12
BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts. Department of Surgery, Harvard Medical School, Boston, Massachusetts.
13
Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Department of Medicine, Harvard Medical School, Boston, Massachusetts. Howard Hughes Medical Institute, Chevy Chase, Maryland. Haber@helix.mgh.harvard.edu.

Abstract

PURPOSE:

The T790M gatekeeper mutation in the EGFR is acquired by some EGFR-mutant non-small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management.

EXPERIMENTAL DESIGN:

As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy. We compared the T790M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells (CTC) and circulating tumor DNA (ctDNA).

RESULTS:

T790M genotypes were successfully obtained in 30 (75%) tumor biopsies, 28 (70%) CTC samples, and 32 (80%) ctDNA samples. The resistance-associated mutation was detected in 47% to 50% of patients using each of the genotyping assays, with concordance among them ranging from 57% to 74%. Although CTC- and ctDNA-based genotyping were each unsuccessful in 20% to 30% of cases, the two assays together enabled genotyping in all patients with an available blood sample, and they identified the T790M mutation in 14 (35%) patients in whom the concurrent biopsy was negative or indeterminate.

CONCLUSIONS:

Discordant genotypes between tumor biopsy and blood-based analyses may result from technological differences, as well as sampling different tumor cell populations. The use of complementary approaches may provide the most complete assessment of each patient's cancer, which should be validated in predicting response to T790M-targeted inhibitors.

PMID:
26446944
PMCID:
PMC4775471
[Available on 2017-03-01]
DOI:
10.1158/1078-0432.CCR-15-1031
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center