Investigators at the University of Texas MD Anderson Cancer Center have found that a 3-drug combination of encorafenib, binimetinib, and cetuximab significantly improved overall survival in patients with BRAF-mutated metastatic colorectal cancer (mCRC). The results of the BEACON CRC phase 3 clinical trial were reported at the ESMO World Congress on Gastrointestinal Cancer 2019.
 
BRAF mutations occur in approximately 15% of patients with mCRC, with V600E being the most common BRAF mutation and representing a poor prognosis for patients. BEACON CRC is the first and only phase 3 trial designed to test BRAF/MEK combination targeted therapies with mCRC, and the BRAF V600E mutation.
 
“This study builds on a decade of research into the tumor biology of BRAF-mutated colorectal cancer and reflects a rationale combination to address the vulnerabilities unique to this tumor,” said Scott Kopetz, MD, principal investigator. “We are encouraged to see a meaningful improvement in outcomes with this new regimen for our patients.”
 
In the open label, 3-arm randomized clinical trial, 665 patients with BRAF V600E-mutant mCRC who had progressed after 1 or 2 prior regimens in the metastatic setting were randomized to receive triplet therapy (encorafenib, binimetinib, and cetuximab), doublet therapy (encorafenib and cetuximab), or the investigator’s choice of irinotecan or folinic acid, fluoruracil and irinotecan (FOLFIRI) and cetuximab.
 
The drug combination was well tolerated with no unexpected toxicities, and grade 3 or higher adverse events were seen in 58% of patients on triplet treatment, 50% in the doublet group, and 61% in the standard therapy group.
 
In August 2018, the FDA granted Breakthrough Therapy Designation to encorafenib, in combination with binimetinib and cetuximab for the treatment of patients with BRAF V600E-mutant mCRC, after failure of one to two prior lines of therapy for metastatic disease.
 
Data from the BEACON CRC trial is being used to support regulatory approval of the triplet combination in metastatic BRAF V600E-mutant mCRC. 
 
Reference
  1. Triplet-targeted therapy improves survival for patients with advanced colorectal cancer and BRAF mutations [press release]. MD Anderson Cancer Center website. Published July 6, 2019. https://www.mdanderson.org/newsroom/triplet-targeted-therapy-improves-survival-for-patients-with-advanced-colorectal-cancer-and-BRAF-mutations.h00-159304623.html. Accessed July 09, 2019.