Encorafenib, cetuximab and binimetinib combined treatment improves survival of patients with advanced colorectal cancer

This study investigated whether treatment with encorafenib (Braftovi), binimetinib (Mektovi), and cetuximab (Erbitux) combined would increase survival in advanced colorectal cancer (CRC). Researchers suggested that this combined therapy increases the survival of patients with metastatic (spread to other parts of the body) CRC.

Colorectal cancer is one of the most common cancers in the US. Around 10% of these patients have a tumor with a BRAF mutation (permanent change). This mutation is associated with more aggressive tumors (faster growth and spread). Initial standard chemotherapy is only of limited effectiveness in these cases. After the failure of first-line treatment, the following lines of treatment have a minimal effect. This leads to disease progression. 

Prior studies showed that treatment with a BRAF inhibitor alone (such as encorafenib) is not sufficient. The combined treatment with BRAF inhibitor and an anti-EGFR antibody (like cetuximab) increases anti-tumor activity. Anti-EGFR antibodies help the immune system to attack and kill cancer cells. However, another study suggested that adding a MEK inhibitor to the therapy results better than an anti-EGFR. MEK inhibitors such as binimetinib stop the action of a specific protein necessary for tumor growth. The effectiveness of this combined treatment with and without MEK inhibitor has never been studied for advanced CRC. 

This study included information about 665 patients with BRAF positive metastatic CRC. These patients progressed after their first-line treatment. Patients were assigned to receive encorafenib and cetuximab with (group 1) and without (group 2) binimetinib. Group 3 consisted of patients who received cetuximab and standard CRC chemotherapy. Overall survival (OS; time from treatment to death by any cause) and response rate were measured. The average follow-up time was 7.8 months.

The average OS was 9 months in group 1 and 5.4 months in group 3. Patients in group 1 had a 48% improvement in the odds of a better OS. The response rate was 26% in group 1, 20% in group 2, and 2% in group 3.

The average in OS in group 2 was 8.4 months. Patients in group 2 had a 40% improvement in the odds of a better OS when compared to group 3.

Moderate side effects occurred in 58% of patients from group 1, 50% from group 2 and 61% in group 3. 7% of patients in group 1 and 8% in group 2 stopped treatment due to side effects. This was compared to 11% in group 3.  

This study concluded that a combination of encorafenib, cetuximab and binimetinib increases survival and tumor response in BRAF-positive, advanced CRC.

This study was funded by Array Biopharma, the manufacturer of binimetinib and encorafenib.