Dr. Lieu on the Predictive Value of BRAF V600E Mutations in mCRC

Christopher Lieu, MD, director, GI Medical Oncology Program and deputy associate director for clinical research, at the University of Colorado Cancer Center, discusses the predictive value of BRAF V600E mutations in metastatic colorectal cancer (mCRC).

Patients who harbor BRAF V600E mutations comprise approximately 5% to 10% of the population with mCRC. This mutation is associated with a poor prognosis due to the aggressive biology of the disease and lack of effective therapies. Historically, some patients with this mutation have an overall survival (OS) that is about one-third of what is normally expected.

However, results from a safety lead-in of the BEACON study were recently published in the Journal of Clinical Oncology. The study looked at the combination of a MEK inhibitor, a BRAF inhibitor, and an EGFR inhibitor: binimetinib (Mektovi), encorafenib (Braftovi), and cetuximab (Erbitux). Investigators noted a response rate of approximately 48%.

Based on these results, investigators launched the phase III study, where patients were randomized to receive the triplet versus standard chemotherapy and an EGFR inhibitor. Data from the trial, which were presented at the 2019 World Congress on Gastrointestinal Cancers, showed a significant improvement in OS with the triplet versus cetuximab and an irinotecan-containing regimen.

The regimen is currently listed in the National Comprehensive Cancer Network (NCCN) guidelines. It's important that providers test for this mutation and that they know that not only is it prognostic, but it could also be predictive of benefit from this treatment, concludes Lieu.