Clinical experience with encorafenib and cetuximab in patients with BRAFV600E-mutant metastatic colorectal cancer after early relapse following adjuvant chemotherapy

Metastatic colorectal cancer (mCRC) is constituted of several biological subgroups characterized by molecular alterations activating specific proliferative pathways. These alterations have, for a long time, lacked targeted therapies capable of inactivating these signalling pathways and eventually modifying the course of the disease. This scenario has rapidly been evolving in recent years, thanks to a better understanding of mCRC biology and advances in drug development, that have turned these alternations into "actionable" targets. BRAFV600E is a landmark example of this process. Conceived for roughly a decade as a negative prognostic factor of outcome and as a predictor of resistance to anti-EGFRs, today it is also a predictor of response to the combination of the anti-BRAF encorafenib and of the anti-EGFR cetuximab, and a standard of care in patients with BRAFV600E-mutated mCRC, after failure of previous systemic therapy. In this work, we report three clinical scenarios where encorafenib and cetuximab are used in label as first-line of treatment, at the diagnosis of mCRC, after early relapse occurring at the end of adjuvant chemotherapy.