Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer

This study reports a prespecified exploratory biomarker analysis of the Phase III PARAGIGM trial, which demonstrated increased overall survival with first-line anti-EGFR (panitumumab) therapy as compared with anti-vascular endothelial growth factor (bevacizumab) therapy in combination with modified FOLFOX6 in RAS wild-type metastatic colorectal cancer patients with left-sided tumors. The utility of negative hyperselection based on gene alterations in circulating tumor DNA (ctDNA) as indicators of primary resistance to anti-EGFR therapy was evaluated. Baseline plasma ctDNA samples from patients in the biomarker study underwent analysis using a custom panel targeting specific gene alterations linked to EGFR resistance (PlasmaSELECT-R 91, Personal Genome Diagnostics). Among 733 assessable patients, those lacking gene alterations exhibited longer overall survival (OS) with panitumumab plus modified FOLFOX6 (median 40.7 vs. 34.4 months) compared to bevacizumab plus modified FOLFOX6. Notably, OS was similar or inferior between the two groups in patients with gene alterations.