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Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses
- Source :
- Clinical Cancer Research. 22:1103-1110
- Publication Year :
- 2016
- Publisher :
- American Association for Cancer Research (AACR), 2016.
-
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. Clin Cancer Res; 22(5); 1103–10. ©2015 AACR.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
Cancer Research
Pathology
medicine.medical_specialty
Genotype
Biopsy
Afatinib
Article
Erlotinib Hydrochloride
03 medical and health sciences
T790M
0302 clinical medicine
Gefitinib
Circulating tumor cell
Carcinoma, Non-Small-Cell Lung
Internal medicine
medicine
Carcinoma
Humans
Protein Kinase Inhibitors
Genotyping
Aged
Aged, 80 and over
medicine.diagnostic_test
business.industry
Cancer
Middle Aged
Neoplastic Cells, Circulating
medicine.disease
respiratory tract diseases
ErbB Receptors
030104 developmental biology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Mutation
Quinazolines
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....df1441111f3dcd7770bc591a8409b527