Early plasma circulating tumor DNA (ctDNA) changes predict response to first-line pembrolizumab-based therapy in non-small cell lung cancer (NSCLC)

Bibliographic Details
Title: Early plasma circulating tumor DNA (ctDNA) changes predict response to first-line pembrolizumab-based therapy in non-small cell lung cancer (NSCLC)
Authors: Mark Awad, Mizuki Nishino, Mariano Severgnini, Biagio Ricciuti, Joao V Alessi, Gonzalo Recondo, Marissa Lawrence, Greg Jones, Tim Forshew, Christine Lydon, Michael Cheng
Source: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 3 (2021)
Publisher Information: BMJ Publishing Group, 2021.
Publication Year: 2021
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Background Currently available biomarkers are imperfect in their ability to predict responses to the multiple first-line treatment options available for patients with advanced non-small cell lung cancer (NSCLC). Having an early pharmacodynamic marker of treatment resistance may help redirect patients onto more effective alternative therapies. We sought to determine if changes in circulating tumor DNA (ctDNA) levels after initiation of first-line pembrolizumab±chemotherapy in NSCLC would enable early prediction of response prior to radiological assessment.Methods Plasma collected from patients with advanced NSCLC prior to and serially after starting first-line pembrolizumab±platinum doublet chemotherapy was analyzed by next-generation sequencing using enhanced tagged-amplicon sequencing of hotspots and coding regions from 36 genes. Early change in ctDNA allele fraction (AF) was correlated with radiographic responses and long-term clinical outcomes.Results Among 62 patients who received first-line pembrolizumab±platinum/pemetrexed and underwent ctDNA assessment, 45 had detectable ctDNA alterations at baseline. The median change in AF at the first follow-up (at a median of 21 days after treatment initiation) was −90.1% (range −100% to +65%) among patients who subsequently had a radiologic response (n=18), –19.9% (range: −100% to +1884%) among stable disease cases (n=15), and +28.8% (range: −100% to +410%) among progressive disease cases (n=12); p=0.003. In addition, there was a significant correlation between the percent change in ctDNA at the first follow-up and the percent change in tumor target lesions from baseline (R=0.66, p
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2051-1426
Relation: https://doaj.org/toc/2051-1426
DOI: 10.1136/jitc-2020-001504
Access URL: https://doaj.org/article/e6145a4c40b5449aabb45da655be4ef6
Accession Number: edsdoj.6145a4c40b5449aabb45da655be4ef6
Database: Directory of Open Access Journals
More Details
ISSN:20511426
DOI:10.1136/jitc-2020-001504
Published in:Journal for ImmunoTherapy of Cancer
Language:English