BRAF and MEK Inhibitor-induced Acute Necrotizing Pancreatitis: A Case Report and Literature Review

Abstract Colorectal cancer (CRC) with the BRAF V600E mutation is an aggressive subtype often resistant to conventional chemotherapy. While B-Raf proto-oncogene (BRAF) / Epidermal growth factor receptor (EGFR) inhibitor combinations are now standard for metastatic BRAF V600E CRC, these BRAF inhibitors can cause various adverse effects. Among these adverse effects, pancreatitis is a rare but serious complication that is often under-recognized due to current trials having limited durations and populations. We report the case of a 50-year-old female with metastatic BRAF V600E-mutant colon cancer who achieved an exceptional and durable complete response over 3 years with off-label dabrafenib and trametinib plus cetuximab. Notably, she developed acute necrotizing pancreatitis after more than 3 years of treatment, a significantly longer latency than previously reported, and experienced recurrence upon rechallenge. A literature review confirmed that pancreatitis is a rare complication across all Food and Drug Administration-approved BRAF inhibitors, with varying onset times. This case highlights the potential for late-onset, severe pancreatitis with prolonged BRAF inhibitor use. Given the increasing use of BRAF inhibitors, particularly in CRC, routine monitoring and further mechanistic research are required.