Results From BEACON CRC Phase 3 Trial Shows That 3 Drug Combo Protocol Effective for BRAF-Mutated Metastatic Colorectal Cancer
Globally, colorectal cancer is the second leading cause of cancer-related deaths. It is expected to cause about 1.8 million deaths during 2019. BRAF mutations are estimated to occur in up to 15 percent of patients with mCRC, with V600 being the most common BRAF mutation and representing a poor prognosis for these patients.
Now Researchers from The University of Texas MD Anderson Cancer Center have concluded based on results from the BEACON CRC Phase III clinical trial that were presented during the ESMO World Congress on Gastrointestinal Cancer 2019 in Barcelona, that the three-drug combination of encorafenib, binimetinib and cetuximab
significantly improved overall survival (OS) in patients with BRAF-mutated metastatic colorectal cancer (mCRC).
The BEACON CRC Clinical trial is the first and only Phase III trial designed to test BRAF/MEK combination targeted therapies in patients with mCRC and the BRAF V600E mutation. BRAF mutations are estimated to occur in up to 15 percent of patients with mCRC, with V600E being the most common BRAF mutation and representing a poor prognosis for these patients.The treatment combination resulted in median OS of 9 months for the combination therapy compared to 5.4 months for current conventional treatment. Objective response rate (ORR) for the triplet-targeted therapy was 26 percent compared to just two percent for current conventional therapy.
Associate Professor(Gastrointestinal Medical Oncology) Scott Kopetz, M.D., principal investigator commented in an exclusive interview with Thailand Medical News,”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.We are encouraged to see a meaningful improvement in outcomes with this new treatment protocol for our patients."
The international study involved a multi-institutional collaboration with over 200 centers globally. In the open label, three-arm randomized clinical trial, 665 patients with BRAF V600E-mutant mCRC who had progressed after one or two prior regimens in the metastatic setting were randomized to receive triplet therapy, doublet therapy (encorafenib and cetuximab) or the investigator's choice of irinotecan or folinic acid., fluoruracil and irinotecan (FOLFIRI) and cetuximab. The triple combination was generally well tolerated with no unexpected toxicities. Grade three or higher adverse events were seen in 58 percent of patients on triplet treatment, 50 percent of those in the doublet group and 61 percent of those in the standard therapy group.
The US FDA in August 2018 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. Results from the BEACON CRC trial is being used to support regulatory approval of the triplet combination in metastatic BRAF V600E-mutant mCRC, and BRAF inhibitor based treatment has recently been included as a treatment option in National Comprehensive Cancer Network (NCCN) guidelines for colon and rectal cancers in America.This targeted therapy combination could be a new standard of care for this patient group.Further investigation is needed to determine if this combination may also benefit those with less advanced disease or as a first-line treatment.