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Advanced colorectal cancer and BRAF mutations: triplet-targeted therapy based on Encorafenib, Binimetinib and Cetuximab, improves survival


The three-drug combination of Encorafenib ( Braftovi ), Binimetinib ( Mektovi ) and Cetuximab ( Erbitux ) has significantly improved overall survival ( OS ) in patients with BRAF-mutated metastatic colorectal cancer ( mCRC ), according to results of the BEACON CRC phase III clinical trial led by researchers at The University of Texas MD Anderson Cancer Center.

The treatment combination resulted in median overall survival of 9 months for the combination therapy compared to 5.4 months for current standard-of-care treatment.
Objective response rate ( ORR ) for the triplet-targeted therapy was 26% compared to just 2% for standard therapy.

BEACON CRC 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% of patients with mCRC, with V600E being the most common BRAF mutation and representing a poor prognosis for these patients.

According to the American Cancer Society ( ACS ), colorectal cancer is the third leading cause of cancer-related deaths in men and in women, and the second most common cause of cancer deaths when men and women are combined.
It is expected to cause about 51,020 deaths during 2019.
BRAF mutations are estimated to occur in up to 15% of patients with mCRC, with V600 being the most common BRAF mutation and representing a poor prognosis for these patients.

The international study was a multi-institutional collaboration with over 200 centers worldwide. 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 triplet combination was generally well tolerated with no unexpected toxicities. Grade three or higher adverse events were seen in 58% of patients on triplet treatment, 50% of those in the doublet group and 61% of those in the standard therapy group.

Source: ESMO World Congress on Gastrointestinal Cancer, 2019

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