Utility of Genomic Assessment of Blood-Derived Circulating Tumor DNA (ctDNA) in Patients with Advanced Lung Adenocarcinoma

Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes. Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 als...

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Bibliographic Details
Published in:Clinical cancer research 2017-09, Vol.23 (17), p.5101-5111
Main Authors: Schwaederlé, Maria C, Patel, Sandip P, Husain, Hatim, Ikeda, Megumi, Lanman, Richard B, Banks, Kimberly C, Talasaz, AmirAli, Bazhenova, Lyudmila, Kurzrock, Razelle
Format: Article
Language:English
Subjects:
Aberration
Adenocarcinoma
Adenocarcinoma - blood
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Adenocarcinoma of Lung
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - blood
Biopsy
Blood
Blood circulation
Circulating Tumor DNA - blood
Clinical trials
Clinical Trials as Topic
Deoxyribonucleic acid
DNA
Epidermal growth factor receptors
Experimental design
Female
Genome, Human - genetics
Genomics
Genotype
Genotyping
High-Throughput Nucleotide Sequencing
Humans
K-Ras protein
Lung Neoplasms - blood
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Lungs
Male
Medical research
Middle Aged
Mutation
Neoplasm Staging
Non-small cell lung carcinoma
p53 Protein
Patients
Therapy
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Description
Summary:Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes. Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 also had tissue next-generation sequencing; 29, other forms of genotyping; and 25 (28.4%) had no tissue molecular tests because of inadequate tissue or biopsy contraindications. Seventy-two patients (82%) had ≥1 ctDNA alteration(s); among these, 75% carried alteration(s) potentially actionable by FDA-approved (61.1%) or experimental drug(s) in clinical trials (additional 13.9%). The most frequent alterations were in the (44.3% of patients), (27.3%), (14.8%), (13.6%), and (6.8%) genes. The concordance rate for alterations was 80.8% (100% vs. 61.5%; ≤1 vs. >1 month between ctDNA and tissue tests; = 0.04) for patients with any detectable ctDNA alterations. Twenty-five patients (28.4%) received therapy matching ≥1 ctDNA alteration(s); 72.3% ( = 16/22) of the evaluable matched patients achieved stable disease ≥6 months (SD) or partial response (PR). Five patients with ctDNA-detected T790M were subsequently treated with a third generation EGFR inhibitor; all five achieved SD ≥ 6 months/PR. Patients with ≥1 alteration with ≥5% variant allele fraction (vs. < 5%) had a significantly shorter median survival ( = 0.012). ctDNA analysis detected alterations in the majority of patients, with potentially targetable aberrations found at expected frequencies. Therapy matched to ctDNA alterations demonstrated appreciable therapeutic efficacy, suggesting clinical utility that warrants future prospective studies. .
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-16-2497