BRAF mutant appendiceal adenocarcinoma differs from colorectal cancer but responds to BRAF-targeted therapy

Appendiceal Adenocarcinoma (AA) is a rare gastrointestinal cancer with no FDA-approved targeted therapies. Here, we retrospectively compare BRAF-mutant AA and colorectal cancer (CRC). BRAF mutation is rare in AA (3%). Unlike CRC, BRAF^V600E AA is not associated with poor prognosis, female sex, microsatellite instability, mucinous histology, or poor differentiation. In both cancers, BRAF^V600E but not atypical BRAF mutations are mutually exclusive with other Ras-activating mutations. BRAF^V600E + EGFR inhibition shows efficacy in BRAF^V600E AA (disease control rate = 80%, median progression-free survival = 7.1 months).