The Food and Drug Administration (FDA) has approved encorafenib (Braftovi) for the treatment of some patients with colorectal cancer. The approval covers the use of encorafenib in combination with cetuximab (Erbitux) in adults with metastatic colorectal cancer whose tumors have a specific mutationin the BRAF gene, called V600E, and who have already undergone at least one prior treatment regimen.
Both drugs are targeted therapies. Cetuximab, which targets a protein known as EGFR, has already been approved to treat some patients with colorectal cancer. Until this new approval, encorafenib, which targets the BRAF protein, was only approved to treat patients with melanoma whose tumors had BRAF mutations.
The new approval was based on findings from a large phase 3 clinical trial, BEACON CRC, that was sponsored by the drug’s manufacturer, Pfizer.
The V600E mutation in the BRAF gene is found in about 10% of metastatic colorectal cancers and is associated with especially poor outcomes. “It’s definitely a group of patients who do not do well with the available therapies, so the availability of this drug combination is definitely a big step forward,” said Carmen Allegra, M.D., special advisor on gastrointestinal cancer therapeutics in NCI’s Division of Cancer Treatment and Diagnosis.
BRAF inhibitors alone have been found to be of limited benefit for patients with BRAF-mutant colorectal cancer, Dr. Allegra explained. “It’s clear that if you just inhibit BRAF, the primary driver of the cancer, the cancer figures out a way around that.”
The BEACON CRC trial was designed to test whether combining targeted therapies to simultaneously block multiple components of the BRAF signaling pathway could improve outcomes in patients with metastatic BRAF-mutant colorectal cancer.
The trial investigators compared both a three-drug combination of encorafenib, cetuximab, and binimetinib (Mektovi) and a two-drug combination of encorafenib and cetuximab with standard chemotherapy plus cetuximab (the control arm). Both combinations were superior to standard treatment, and the two-drug combination was just as effective as the three-drug regimen.
Patients who received encorafenib and cetuximab had a median overall survival of 8.4 months compared with 5.4 months for patients in the control arm. Also, more patients who received the two-drug combination had reductions in the size of their tumors (a tumor response) than patients in the control arm: 20% versus 2%.
The trial “is teaching us something about how to use these targeted therapies,” Dr. Allegra said.
The most common severe side effects in patients treated with encorafenib and cetuximab included fatigue and weakness. Other common reactions included nausea, rash, and diarrhea.