Upfront progression under pembrolizumab followed by a complete response after encorafenib and cetuximab treatment in BRAF V600E‐mutated and microsatellite unstable metastatic colorectal cancer patient: A case report

Abstract

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.