ASCO GI 2022 | The rationale behind the addition of immunotherapy to TKIs in treating BRAFV600E mutated mCRC

Van K. Morris, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, dicusses the additon of immunotherpay to the treatment of BRAFV600E mutated microsatellite-stable (MSS) metastatic colorectal cancer (CRC) with tyrosine kinase inhibitros (TKIs). Dr. Morris notes that these tumor exhibit higher levels of immunological activity than their counterparts, and are often characterized by higher mutation burden that produces increased levels of neoepitopes and neoantigens that are recognized by the immune system. The tumors are additionally characterized by higher rates of consensus molecular subtype 1, an RNA-based transcriptomic signature known to demonstrate higher immune activation. Preclinical work has looked into an MSS BRAFV600E mutated CRC cell line treated with BRAF-EGFR inhibitors in cell culture which illustrated a decreased expression of the four DNA mismatch repair (MMR) genes and induced a microsatellite instability (MSI) – high phenotype. If this were to be translated to humans, it would be expected that treatments such as encorafinib and cetuximab would prime these tumors for an effective response to immunotherapy. This will be investigated in correlative studies in the translational analysis of paired specimens in a clinical trial. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2022.