Publication
Title
Impact of emergent circulating tumor DNA RAS mutation in panitumumab-treated chemoresistant metastatic colorectal cancer
Author
Abstract
Purpose: The accumulation of emergent RAS mutations during anti-EGFR therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine RAS mutational status. Experimental Design: This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded RAS ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of RAS mutations by the PlasmaSelect-R 64-gene panel at 0.1% sensitivity. Results: Among panitumumab-treated patients with evaluable plasma samples at baseline (n = 238), 188 (79%) were wild-type (WT) RAS, and 50 (21%) were mutant RAS. Of the 188 patients with baseline ctDNA WT RAS status, 164 had evaluable posttreatment results with a 32% rate of emergent RAS mutations. The median overall survival for WT and RAS mutant status by ctDNA at baseline was 13.7 (95% confidence interval, 11.5-15.4) and 7.9 months (6.4-9.6), respectively (P < 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA RAS mutations. Conclusions: Although patients with baseline ctDNA RAS mutations had worse outcomes than patients who wereWT RAS before initiating treatment, emergent ctDNA RAS mutations were not associated with less favorable patient outcomes in panitumumab-treated patients. Further research is needed to determine a clinically relevant threshold for baseline and emergent ctDNA RAS mutations. (C) 2018 AACR.
Language
English
Source (journal)
Clinical cancer research. - Philadelphia, Pa, 1995, currens
Publication
Philadelphia, Pa : Association for Cancer Research , 2018
ISSN
1078-0432 [print]
1557-3265 [online]
Volume/pages
24 :22 (2018) , p. 5602-5609
ISI
000450349300014
Pubmed ID
29898991
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
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Creation 10.12.2018
Last edited 20.09.2021
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