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

The accumulation of emergent 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 mutational status. This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of mutations by the Plasma-R 64-gene panel at 0.1% sensitivity. Among panitumumab-treated patients with evaluable plasma samples at baseline ( = 238), 188 (79%) were wild-type (WT) , and 50 (21%) were mutant Of the 188 patients with baseline ctDNA WT status, 164 had evaluable posttreatment results with a 32% rate of emergent mutations. The median overall survival for WT and 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 ( < 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA mutations. Although patients with baseline ctDNA mutations had worse outcomes than patients who were WT before initiating treatment, emergent ctDNA 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 mutations. .