Updates in BRAF V600E-Mutated Metastatic Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide, and the second leading cause of cancer death. Approximately one in five patients with CRC present with metastatic disease at diagnosis. The BRAF V600E mutation occurs in 8–12% of patients with metastatic colorectal cancer (mCRC), and is characterised by an aggressive clinical course and poor prognosis. This article is based on a webinar discussion in March 2024, between two experts in gastrointestinal cancers, Chiara Cremolini, University of Pisa, Italy; and Julien Taieb, Georges Pompidou European Hospital, Université Paris-Cité, France, both of whom have a wealth of experience and expertise in the clinical management of CRC. The experts described the most important recent advances in the treatment of BRAF V600E-mutated mCRC, including data presented at the European Society for Medical Oncology (ESMO) Congress in October 2023, and the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in January 2024. Cremolini and Taieb gave valuable insights into topics such as the aggressive nature of BRAF V600E-mutated mCRC, and how this impacts choice of treatment, patient outcomes, and quality of life, as well as the importance of early testing and monitoring. The experts also discussed how the BRAF V600E mutation impacts treatment response and outcomes in patients with microsatellite unstable (microsatellite instability [MSI]) versus microsatellite stable (MSS) tumours, and recent key clinical trials in BRAF V600E-mutated mCRC. The importance of surgery in the multidisciplinary management of patients with BRAF V600E-mutated mCRC, BRAF as a prognostic marker in resected CRC, and real-world studies in this field were also explored. Finally, Cremolini and Taieb described what the future of the management of patients with BRAF V600E-mutated mCRC might look like, and which advancements in research they would like to see.