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Utility of liquid biopsies to assess circulating tumor DNA in patients with lung adenocarcinoma.
Background: Liquid biopsies were used to assess genomic alterations in plasma circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC), and therapeutic outcomes analyzed. Methods: ctDNA testing (digital next-generation sequencing (NGS)) was performed in 88 patients with advanced NSCLC; (54 or 68 gene panel; 40 and 48 patients, respectively (Guardant Health, Inc. (Guardant360 test))) (Clinical Laboratory Improvement Amendment (CLIA) laboratory). Fifty-five patients (62.5%) also had some tissue molecular testing, 37 of whom had a consistent tissue NGS panel ( ≥ 182-genes). Results: Eighty-two percent of patients (72/88) had ≥ 1 ctDNA alteration(s) (median = 2 alterations), most frequently TP53 (44.3% of patients), EGFR (27.3%), MET (14.8%), KRAS (13.6%), and ALK (6.8%). Retrospective analysis showed that 25 of 88 patients (28.4%) had received a therapy matching at least one ctDNA alteration(s) (most frequently an inhibitor of EGFR (N = 18), ALK, BRAF, other). Sixty-five percent of evaluable (N = 5 patients, too early) matched patients (N = 13/20) achieved stable disease (SD) ≥ 6 months or partial response (PR). The median progression-free survival for the 25 matched patients was 13.9 months. For the 37 patients who had both the tissue NGS panel and the ctDNA test (median 1.3 months (range, 0.1 to 20.9) between tissue biopsy and blood draw), the concordance rate for EGFR ctDNA alterations with tissue NGS was 70.3% (k = 0.361), with higher concordance when time interval between tissue and blood tests was ≤ 1.3 months. When we only considered patients in whom ctDNA confirmed present (N = 27), the EGFR concordance was 77.8% (k = 0.526). Fifty-one patients (58%) did not have the tissue NGS test performed, including 33 (37.5%) who had no other tissue molecular testing, usually because of inadequate tissue or potential morbidity for repeat biopsy. Conclusions: ctDNA frequently revealed genomic alterations in NSCLC adenocarcinoma, including in difficult-to-biopsy patients. Patients who received cognate therapies demonstrated a high rate of SD ≥ 6months/PR, suggesting clinical utility.
Abstracts by Maria Clemence Schwaederle:
Impact of precision medicine in refractory malignancies: A meta-analysis of 13,203 patients in phase I clinical trials.Meeting: 2016 ASCO Annual Meeting | Abstract No: 11520
Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor DNA assay.Meeting: 2015 ASCO Annual Meeting | Abstract No: 11004
Presentations by Maria Clemence Schwaederle:
Detection Rate of Actionable Mutations in Diverse Cancers Using a Biopsy-Free (Blood) Circulating Tumor DNA AssayMeeting: 2015 ASCO Annual Meeting Abstract No: 11004Session: Tumor Biology (Oral Abstract Session)