Garcia-Alfonso P, et al. - Researchers performed a trial of regorafenib in patients with RAS- or BRAF-mutated metastatic colorectal cancer (mCRC) progressing on first-line bevacizumab plus 5-FU/irinotecan/oxaliplatin (FOLFOXIRI). They focused on 6-month progression-free survival (PFS) in patients who were administered regorafenib daily for 3 weeks of each 4-week cycle until disease progression or other reason. Although stopped prematurely for failing to accrue, regorafenib had acceptable tolerability but no clinical activity in KRAS- or BRAF-mutated mCRC with progression following first-line with FOLFOXIRI plus bevacizumab. The most common regorafenib-related grade 3 adverse events (AEs) were asthenia (33%), dysphonia (13%), and hypertension (13%). This study suggests better population refinement is needed to explore regorafenib efficacy in an earlier line of therapy.