Durable complete response to pembrolizumab after BRAF/MEK inhibition in recurrent MSI-H/dMMR, BRAF V600E–mutant colon cancer: a case report

Patients with metastatic colorectal cancer (mCRC) harboring both microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) and the BRAF V600E mutation represent a distinct clinicomolecular subgroup characterized by aggressive biology and distinct therapeutic challenges. While MSI-H/dMMR predicts sensitivity to immune checkpoint inhibitors (ICIs), the concurrent BRAF V600E mutation may contribute to secondary resistance or shortened durability of response in a subset of patients treated with ICI monotherapy. Here, we present the case of an 85-year-old female with locally advanced ascending colon cancer who experienced rapid recurrence and metastasis only four months after radical surgery. Molecular profiling confirmed MSI-H, dMMR, and BRAF V600E mutation. Given her advanced age and frailty, she was treated with a first-line combination of pembrolizumab, dabrafenib, and trametinib. Although the targeted therapy (dabrafenib/trametinib) was discontinued after approximately two months due to recurrent high-grade pyrexia, the patient continued on pembrolizumab maintenance. She achieved a radiographic complete response (CR) and has remained progression-free for over 26 months. This case highlights the potential synergy between MAPK pathway inhibition and immunotherapy, suggesting that even short-course targeted therapy may favorably remodel the tumor microenvironment to enable durable disease control in high-risk MSI-H/BRAF-mutant mCRC.