encorafenib and Microsatellite-Instability

Two new treatments have recently become standard care for patients with metastatic colorectal cancer (mCRC): encorafenib (BRAF inhibitor) associated with cetuximab (anti-EGFR) in the second or third line of chemotherapy for BRAF V600E tumors, and pembrolizumab (an anti PD-1 immune checkpoint inhibitor) for tumors harboring microsatellite instability (MSI)-high and/or deficient mismatch repair (dMMR). Furthermore, 30% of BRAF V600E mutated mCRC are MSI/dMMR through a sporadic hypermethylation of the promoter of hMLH1. We report here, for the first time, the case of a patient with BRAF V600E, PIK3CA, and SMAD4 mutated and dMMR/MSI mCRC, in whom we observed an atypical response pattern under the sequence of pembrolizumab followed by the doublet encorafenib and cetuximab treatment. The patient was progressive after a single cycle of pembrolizumab followed by a rapid complete response after only 2 months of treatment with encorafenib and cetuximab, discovered during R0 cytoreduction surgery for peritoneal carcinomatosis.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carbamates; Cetuximab; Colon; Colorectal Neoplasms; Disease Progression; DNA Methylation; Female; Humans; Immunotherapy; Microsatellite Instability; Middle Aged; Mutation; Proto-Oncogene Proteins B-raf; Sulfonamides

Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAF. Anonymized data from BRAF. Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAF

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carbamates; Cetuximab; Colorectal Neoplasms; Female; Humans; Male; Microsatellite Instability; Middle Aged; Mutation; Proto-Oncogene Proteins B-raf; Retrospective Studies; Sulfonamides