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

Sep 22, 2026

The activating BRAF V600E mutation is present in 8%–12% of metastatic colorectal cancers and is linked to peritoneal carcinomatosis with poor outcomes. Encorafenib plus cetuximab targeting EGFR and FOLFOX chemotherapy has shown benefit in phase III BREAKWATER and FDA approval in 2025. This report describes a 26-year-old man with BRAF V600E–mutant microsatellite-stable rectal cancer, liver metastases, and peritoneal carcinomatosis presenting with bowel obstruction and inability to take oral drugs. Encorafenib was administered rectally and via nasogastric tube with FOLFOX+EC. Adverse events occurred largely before treatment, improved during therapy, and severe events were mainly emesis, fatigue, pain, and cholestatic liver enzyme elevations. Pharmacokinetics showed trough exposure comparable to oral dosing without peritoneal carcinomatosis, and imaging at weeks 4 and 8 demonstrated early tumor shrinkage, with objective and clinical remission. Short-term safety appeared manageable, though infection risk could not be excluded.

LanguageEnglish

CategoryHealthcare

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Pages7

Reading Time18 min

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Abstract

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The Oncologist, 2026, 31, oyag103 [https://doi.org/10.1093/oncolo/oyag103](https://doi.org/10.1093/oncolo/oyag103) [Published: 31 March 2026](Published: 31 March 2026) Precision Medicine Clinic: Molecular Tumor Board Gastric and rectal administration of encorafenib with targeted chemotherapy against BRAF V600E–mutant rectal cancer with bowel obstruction Maximilian Alexander Funk*,1,2,3,4, , Volker Heinemann2, , Veit B €ucklein1,2,4, , Stefan Karl Alig5,6, , Kathrin Heinrich1,2,3,4, , Lena Weiss1,2,3,4, Victoria Krenmayr1,2,3,4, Benoit Blanchet7,8, , Wolfgang Gerhard Kunz9, Sebastian Theurich1,2,3,4, , Michael von Bergwelt-Baildon1,2,3,4, Julian Walter Holch1,2,3,4, 1 Department of Medicine III, LMU University Hospital Munich, Munich, 81377, Germany 2Comprehensive Cancer Center Munich, Munich, 81377, Germany 3German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Munich, 80336, Germany 4 Bavarian Cancer Research Center (BZKF), Munich, 81377, Germany 5 Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, 45147, Germany 6German Cancer Consortium (DKTK), Partner Site Essen and German Cancer Research Centre (DKFZ), Heidelberg, Essen, 45147, Germany 7Service de Biologie du Mdicament et Toxicologie, CARPEM, H^opital Cochin, AP-HP, Paris, Paris, 75014, France 8 Universit Paris Cit CNRS, INSERMCiTCoM, Paris, 75006, France 9 Department of Radiology, LMU University Hospital Munich, Munich, 81377, Germany *Corresponding author: Maximilian A. Funk, Department of Medicine III, LMU University Hospital Munich, Munich Germany (maximilian.funk@med. [uni-muenchen.de](uni-muenchen.de)) . Abstract 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. Treatmentrelated 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. Key words: metastatic colorectal cancer; BRAF mutation; peritoneal carcinomatosis; encorafenib; bowel obstruction Received: December 21, 2025. Accepted: March 14, 2026 © The Author(s) 2026. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)), which permits unrestricted reuse, distribution, and reproduction in any medium, p

FAQs

Why is targeted BRAF inhibition challenging in patients with peritoneal carcinomatosis and bowel obstruction?

Bowel obstruction can prevent oral drug administration, creating a barrier to delivering encorafenib in the usual route. In peritoneal carcinomatosis, this obstacle is particularly relevant for treatment planning.

How was encorafenib administered in this case to enable targeted therapy?

Encorafenib was given rectally and via a nasogastric tube. This was combined with intravenous cetuximab and standard chemotherapy FOLFOX (FOLFOX+EC).

What safety and pharmacokinetic findings were reported during treatment?

Most adverse events were present before therapy and improved during FOLFOX+EC; severe events included emesis, fatigue, pain, and elevated cholestatic liver enzymes. Pharmacokinetic analysis showed trough plasma exposure comparable to oral dosing in patients without peritoneal carcinomatosis.

Sep 22, 2026

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