A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in EGFR-Mutant Non–Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial
Open Access
- 15 December 2016
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 22 (24), 6010-6020
- https://doi.org/10.1158/1078-0432.ccr-16-0909
Abstract
Background: Genotype-directed therapy is standard-of-care for advanced NSCLC, but obtaining tumor tissue for genotyping remains a challenge. CTC or cfDNA analysis may allow for noninvasive evaluation. This prospective trial evaluated CTCs and cfDNA in EGFR-mutant NSCLC patients treated with erlotinib until progression. Methods: EGFR-mutant NSCLC patients were enrolled in a phase II trial of erlotinib. Blood was collected at baseline, every 2 months on study, and at disease progression. Plasma genotyping was performed by droplet digital PCR for EGFR19del, L858R, and T790M. CTCs were isolated by CellSave, enumerated, and analyzed by immunofluorescence for CD45 and pan-cytokeratin and EGFR and MET FISH were. Rebiopsy was performed at disease progression. Results: 60 patients were enrolled; 44 patients discontinued therapy for disease progression. Rebiopsy ocurred in 35/44 patients (80%), with paired CTC/cfDNA analysis in 41/44 samples at baseline and 36/44 samples at progression. T790M was identified in 23/35 (66%) of tissue biopsies and 9/39 (23%) of cfDNA samples. CTC analysis at progression identified MET amplification in 3 samples in which tissue analysis could not be performed. cfDNA analysis identified T790M in 2 samples in which rebiopsy was not possible. At diagnosis, high levels of cfDNA but not high levels of CTCs correlated with progression-free survival.. Conclusions: cfDNA and CTCs are complementary, noninvasive assays for evaluation of acquired resistance to first-line EGFR TKIs and may expand the number of patients in whom actionable genetic information can be obtained at acquired resistance. Serial cfDNA monitoring may offer greater clinical utility than serial monitoring of CTCs.Other Versions
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