Monitoring of EGFR mutations in circulating tumor DNA of non-small cell lung cancer patients treated with EGFR inhibitors
Verheijen, R. B.; van Duijl, T. T.; van den Heuvel, M. M.; Vessies, D.; Muller, M.; Beijnen, J. H.; Janssen, J. M.; Schellens, J. H.M.; Steeghs, N.; van den Broek, D.; Huitema, A. D.R.
(2021) Cancer Chemotherapy and Pharmacology, volume 87, issue 2, pp. 269 - 276
(Article)
Abstract
Purpose: We studied EGFR mutations in circulating tumor DNA (ctDNA) and explored their role in predicting the progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients treated with erlotinib or gefitinib. Methods: The L858R, T790M mutations and exon 19 deletions were quantified in plasma using digital droplet polymerase chain
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reaction (ddPCR). The dynamics of ctDNA mutations over time and relationships with PFS were explored. Results: In total, 249 plasma samples (1–13 per patient) were available from 68 NSCLC patients. The T790M and L858R or exon 19 deletion were found in the ctDNA of 49 and 56% patients, respectively. The median (range) concentration in these samples were 7.3 (5.1–3688.7), 11.7 (5.1–12,393.3) and 27.9 (5.9–2896.7) copies/mL, respectively. Using local polynomial regression, the number of copies of EGFR mutations per mL increased several months prior to progression on standard response evaluation. Conclusion: This change was more pronounced for the driver mutations than for the resistance mutations. In conclusion, quantification of EGFR mutations in plasma ctDNA was predictive of treatment outcomes in NSCLC patients. In particular, an increase in driver mutation copy number could predict disease progression.
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Keywords: ctDNA, EGFR, Erlotinib, Gefitinib, Liquid biopsy, NSCLC, Circulating Tumor DNA/genetics, Humans, Middle Aged, Erlotinib Hydrochloride/administration & dosage, Male, Treatment Outcome, ErbB Receptors/antagonists & inhibitors, Protein Kinase Inhibitors/administration & dosage, Gefitinib/administration & dosage, Lung Neoplasms/drug therapy, Progression-Free Survival, Carcinoma, Non-Small-Cell Lung/drug therapy, Drug Resistance, Neoplasm/genetics, Aged, 80 and over, Adult, Female, Aged, Mutation, Pharmacology (medical), Oncology, Cancer Research, Toxicology, Pharmacology, Observational Study, Journal Article
ISSN: 0344-5704
Publisher: Springer-Verlag
Note: Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
(Peer reviewed)