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Clin Cancer Res. 2018 Jun 13. pii: clincanres.3377.2017. doi: 10.1158/1078-0432.CCR-17-3377. [Epub ahead of print]

Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer.

Author information

1
Oncology, Asan Medical Center, University of Ulsan College of Medicine.
2
Department of Oncology, Antwerp University Hospital.
3
Cancer Research Centre, University of Leicester.
4
Department of Medical Oncology and Haematology, Royal Melbourne Hospital.
5
Amgen Inc.
6
Medical Sciences Early Development, Amgen Inc.
7
Global Development, AbbVie Inc.
8
Oncology, The Queen Elizabeth Hospital Timothy.Price@sa.gov.au.

Abstract

PURPOSE:

The accumulation of emergent RAS mutations during anti-epidermal growth factor receptor (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 (OS) 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 were WT 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.

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