Acquired resistance to first-line chemo- and EGFRab-therapy in mCRC: Biopsy analysis of the iSCORE trial

Abstract

Background: Anti-epidermal growth factor receptor antibodies (EGFRabs) such as cetuximab/panitumumab are effective treatments for RAS/RAF wild-type (wt) metastatic colorectal cancer (mCRC). Acquired resistance (AR) to single-agent EGFRabs frequently occurs through genetic aberrations (GAs) that reactivate the RAS/RAF pathway. Surprisingly, only 6.6% of patients (pts) in the SWOG-80405 trial had mutations (MTs) that activate the RAS/RAF pathway in their ctDNA after first line chemo- and EGFRab combination-therapy. This may suggest that AR differs when EGFRabs are given with chemo- compared to monotherapy. Here, we report the analysis of genetic AR in biopsies from mCRCs that progressed on EGFRab and chemotherapy.