Gastric and rectal administration of encorafenib with targeted chemotherapy against BRAF V600E–mutant rectal cancer with bowel obstruction

The activating BRAF mutation V600E occurs in 8%-12% of metastatic colorectal cancers (mCRC) and is associated with peritoneal carcinomatosis (PC) and poor prognosis. Targeted inhibition with the oral BRAF inhibitor encorafenib, combined with intravenous cetuximab targeting epithelial growth factor receptor (EGFR) and standard chemotherapy FOLFOX, has improved outcomes and received FDA approval in 2025 based on results from the phase III BREAKWATER trial. We report a 26-year-old male with rapidly progressive, BRAF V600E-mutant, microsatellite-stable (MSS) rectal adenocarcinoma, liver metastases, and PC presenting with bowel obstruction and inability for oral intake. To enable targeted therapy, encorafenib was administered rectally and via nasogastric tube, together with intravenous cetuximab and FOLFOX (FOLFOX+EC). Most adverse events (AEs) were present before treatment and improved during FOLFOX+EC, indicating tumor association. Severe AEs included emesis, fatigue, pain, and elevated cholestatic liver enzymes. Treatment-related AEs were manageable with anaemia (°3), neutropenia (°4), and thrombocytopenia (°1). No encorafenib-specific toxicities (rash, pyrexia, QTc prolongation, or ocular effects) were observed. Pharmacokinetic analysis showed trough plasma exposure comparable to oral dosing in patients without PC, and CT imaging at weeks 4 and 8 revealed early tumor shrinkage. This case demonstrates that rectal and nasogastric administration of encorafenib is feasible, achieves therapeutic plasma concentrations, and induces objective and clinical remission in the context of FOLFOX+EC. Short-term safety appeared manageable, though increased infection risk cannot be excluded.