Back to Search
Start Over
Analysis of circulating tumour DNA to identify patients with epidermal growth factor receptor-positive non-small cell lung cancer who might benefit from sequential tyrosine kinase inhibitor treatment.
- Source :
-
European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2021 May; Vol. 149, pp. 61-72. Date of Electronic Publication: 2021 Apr 05. - Publication Year :
- 2021
-
Abstract
- Background: Survival data support the use of first-line osimertinib as the standard of care for epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC). However, it remains unclear whether upfront osimertinib is superior to sequential first- or second-generation tyrosine kinase inhibitors (TKIs) followed by osimertinib for all patients. It is impossible to predict which patients are at high risk of progression, and this constitutes a major limitation of the sequential TKI approach.<br />Patients and Methods: A total of 830 plasma samples from 228 patients with stage IV, EGFR-positive NSCLC who were treated with first-line TKIs were analysed by digital polymerase chain reaction (dPCR).<br />Results: The circulating tumour DNA (ctDNA) levels helped to identify patients with significantly improved survival rate, regardless of the treatment. Patients treated with first- or second-generation TKIs (N = 189) with EGFR mutations in plasma at a mutant allele frequency (MAF) <7% before treatment initiation (low-risk patients) or who were ctDNA negative after 3 or 6 months of treatment and with an MAF <7% at diagnosis (high responders) had two-thirds lower risk of death than patients in the opposite situation (adjusted hazard ratio [HR] = 0.38; 95% confidence interval [CI]: 0.23-0.64 and HR = 0.22; 95% CI: 0.12-0.42, respectively). The median overall survival (OS) for low-risk patients and high responders treated with first- or second-generation TKIs was 34.2 months and not reached, respectively, regardless of second-line treatment. There were no significant difference in OS between low-risk or high-responder patients treated upfront with osimertinib (N = 39) and those treated under a sequential approach with osimertinib (N = 60). Median OS was not reached in both cases.<br />Conclusions: Pre-treatment ctDNA levels identify low-risk patients, who may benefit from sequential TKI treatment. Information regarding EGFR mutation clearance can help to improve patient selection.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Acrylamides therapeutic use
Aged
Aniline Compounds therapeutic use
Antineoplastic Agents therapeutic use
Biomarkers, Tumor antagonists & inhibitors
Biomarkers, Tumor blood
Carcinoma, Non-Small-Cell Lung blood
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung pathology
Circulating Tumor DNA blood
Clinical Decision-Making
Cross-Sectional Studies
DNA Mutational Analysis
ErbB Receptors antagonists & inhibitors
ErbB Receptors blood
ErbB Receptors genetics
Female
Humans
Lung Neoplasms blood
Lung Neoplasms drug therapy
Lung Neoplasms pathology
Male
Middle Aged
Neoplasm Staging
Polymerase Chain Reaction
Predictive Value of Tests
Prospective Studies
Protein Kinase Inhibitors therapeutic use
Spain
Time Factors
Treatment Outcome
Biomarkers, Tumor genetics
Carcinoma, Non-Small-Cell Lung genetics
Circulating Tumor DNA genetics
Lung Neoplasms genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0852
- Volume :
- 149
- Database :
- MEDLINE
- Journal :
- European journal of cancer (Oxford, England : 1990)
- Publication Type :
- Academic Journal
- Accession number :
- 33831609
- Full Text :
- https://doi.org/10.1016/j.ejca.2021.02.031