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: 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.
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Authors | Tilak K Sundaresan, Lecia V Sequist, John V Heymach, Gregory J Riely, Pasi A Jänne, Walter H Koch, James P Sullivan, Douglas B Fox, Robert Maher, Alona Muzikansky, Andrew Webb, Hai T Tran, Uma Giri, Martin Fleisher, Helena A Yu, Wen Wei, Bruce E Johnson, Thomas A Barber, John R Walsh, Jeffrey A Engelman, Shannon L Stott, Ravi Kapur, Shyamala Maheswaran, Mehmet Toner, Daniel A Haber |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 22
Issue 5
Pg. 1103-10
(Mar 01 2016)
ISSN: 1557-3265 [Electronic] United States |
PMID | 26446944
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | ©2015 American Association for Cancer Research. |
Chemical References |
- Protein Kinase Inhibitors
- Quinazolines
- Afatinib
- Erlotinib Hydrochloride
- EGFR protein, human
- ErbB Receptors
- Gefitinib
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Topics |
- Adult
- Afatinib
- Aged
- Aged, 80 and over
- Biopsy
- Carcinoma, Non-Small-Cell Lung
(blood, genetics, pathology)
- Drug Resistance, Neoplasm
(genetics)
- ErbB Receptors
(blood, genetics)
- Erlotinib Hydrochloride
(administration & dosage)
- Female
- Gefitinib
- Genotype
- Humans
- Male
- Middle Aged
- Mutation
- Neoplastic Cells, Circulating
(drug effects)
- Protein Kinase Inhibitors
(administration & dosage)
- Quinazolines
(administration & dosage)
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