Comprehensive Treatment of Colorectal Cancer with MSI and BRAF Mutation: From Surgery to Personalized Immune Targeted Therapy. Clinical Case

Abstract

Introduction. Colorectal cancer (CRC) is a very heterogeneous group of diseases. Molecular analysis for the presence of somatic mutations in the RAS gene family (KRAS/NRAS/BRAF) and the determination of MSI/dMMR status in patients with metastatic colorectal cancer (mCRC) are included in the standard diagnostic algorithm according to Russian and international guidelines for cancer diagnosis and treatment. While treatment standards for wild-type tumors are well established, approaches for diseases with combined biological types and mutations are not fully defined. For example, chemotherapy remains the standard treatment for BRAF-mutant CRC. However, due to the poor prognosis of this patient group, numerous clinical trials are underway to find a combined, targeted approach. Currently, there are treatment standards for patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) and for patients with BRAF mutations. However, no treatment standards have yet been developed for patients with both MSI-H and BRAF mutations. Active research is underway to develop combined approaches, including immunotherapy and targeted therapy.

Case Description. We present a clinical case of the treatment of colorectal cancer with MSI and BRAF mutation. An attempt was made to use a combined immune targeted approach to achieve the best objective response. A short period of treatment with a BRAF inhibitor and an anti-PD-1 drug resulted in a greater response compared with monotherapy. However, the therapy was subsequently de-escalated due to the onset of toxicity.

Conclusion. Our experience demonstrates the need for more active research and exploration of combined treatment regimens to improve outcomes for patients with rare biological tumors. However, attention should be paid to the potential toxicity of combined approaches.