A recent study evaluated the benefit of a new combination treatment for patients with BRAF-mutant metastatic colorectal cancer.
Approximately ten percent of patients with metastatic colorectal cancer have the BRAF mutation. This specific colorectal cancer subtype carries a poor prognosis as initial treatment for BRAF-mutated metastatic colorectal cancer often has poor outcomes and next line treatments have minimal effect.
Recent evidence has identified that inhibition of the BRAF-mutated pathway alone during treatment is not enough, which explains the lackluster clinical efficacy seen with current BRAF-inhibiting treatments. BRAF inhibitors, however, have been shown to be more effective against cancer activity when combined with an anti-EGFR monoclonal antibody. This was demonstrated in initial phase clinical trials. Further, initial trials of a triple combination treatment that also included a MEK inhibitor agent showed promise against BRAF-mutated metastatic colorectal cancer.
To study whether the triple therapy combination would improve overall survival in patients with BRAF-mutated metastatic colorectal cancer, a team of researchers designed and conducted the BEACON CRC (Binimetinib, Encorafenib, and Cetuximab Combined to Treat BRAF-Mutant Colorectal Cancer) trial. Their results are published in the New England Journal of Medicine.
BEACON CRC is a global, multi-center, phase three, randomized trial that included 665 patients with BRAF-mutated metastatic colorectal cancer who had treatment failure after either the first or second treatment lines. Patients were randomized to one of three treatment groups: triple therapy group (receiving encorafenib, binimetinib, and cetuximab), double therapy group (encorafenib and cetuximab), or the control group (a standard treatment of the investigator’s choice). This triple therapy combination was designed to be the most effective at targeting the BRAF-mutated metastatic colorectal cancer pathways. The researchers focused on the overall survival and the objective response rate of the tumour to treatment between the triple therapy and control groups.
The findings demonstrated a significant, 48%, lower risk of death in the triple therapy group compared to the control group, where the triple therapy group’s median overall survival rate was 9 months compared to 5.4 months in the control. There was also a much higher objective response rate in the triple therapy group (26%) and the double therapy group (20%) than the control group (2%). A longer duration of time before disease progression was observed in the triple and double therapy groups at a median of 4.3 and 4.2 months, respectively, whereas control group patients had disease progression after a median 1.5 months.
The adverse effects seen among all groups were as expected for the drug profiles and the combination therapy groups did not see greater toxicity or death compared to control.
Early analysis of the BEACON CRC trial results demonstrates a longer overall survival and higher objective response rate with a triple therapy combination of encorafenib, binimetinib, and cetuximab compared to standard treatment. This is promising for the future of treatment options to improve outcomes for patients with the BRAF-mutated metastatic colorectal cancer. The benefits of this triple therapy should be further studied in future trials.
Written by Maggie Leung, PharmD.
Kopetz, S., Grothey, A., Yaeger, R., Cutsem, E. V., Desai, J., Yoshino, T., … Tabernero, J. (2019). Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer. New England Journal of Medicine. doi: 10.1056/nejmoa1908075
Novel treatment combination for patients with BRAF-mutant metastatic colorectal cancer. (2019, September 30). Retrieved from https://www.eurekalert.org/pub_releases/2019-09/vdio-ntc093019.php.
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