Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses
| Autor: | Martin Fleisher, Walter H. Koch, Pasi A. Jänne, Jeffrey A. Engelman, Shyamala Maheswaran, Alona Muzikansky, Helena A. Yu, Bruce E. Johnson, Andrew Webb, Mehmet Toner, Gregory J. Riely, Daniel A. Haber, James P. Sullivan, John V. Heymach, Wen Wei, Ravi Kapur, Tilak K. Sundaresan, Uma Giri, Robert C. Maher, Douglas B. Fox, Hai T. Tran, John R. Walsh, Tom Barber, Lecia V. Sequist, Shannon L. Stott |
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| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | Clinical Cancer Research. 22:1103-1110 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-15-1031 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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