From Crisis to Cure: A Case Report of Pathologic Complete Response in a Young Male with BRAF-mutant dMMR Metastatic Colorectal Cancer after Immunotherapy

Abstract Metastatic colorectal cancer (mCRC) with a BRAF V600E mutation is an aggressive subtype with poor prognosis and limited response to standard chemotherapy. However, coexisting deficient mismatch repair (dMMR) is associated with improve outcomes with immunotherapy. We present the case of early-onset BRAF V600E -mutated dMMR mCRC in a 38-year-old male diagnosed in 2019. After progression on FOLFIRINOX plus bevacizumab and intolerance to second-line targeted therapy with cetuximab/dabrafenib/trametinib, he began third-line treatment with nivolumab and low-dose regorafenib in June 2020. A remarkable clinical and pathological response was achieved, with complete tumor regression and no recurrence for over 4 years. This case highlights the potential for a dramatic response in BRAF-mutated dMMR mCRC through early immunotherapy, and that the combination of low-dose regorafenib and nivolumab may offer a synergistic effect. The early use of immune checkpoint blockade should be considered in this subset of patients, and further studies are needed to optimize treatment sequencing.