BEACON CRC: encorafenib and cetuximab with or without binimetinib in BRAF V600E-mutated colorectal cancer
Blocking BRAF with encorafenib and EGFR with cetuximab lengthened survival compared with standard chemotherapy in previously treated BRAF V600E-mutant colorectal cancer, the first targeted regimen to work in this poor-prognosis group.
Overview
Phase 3 trial of 665 patients with BRAF V600E-mutated metastatic colorectal cancer after one or two prior regimens randomised to encorafenib, binimetinib and cetuximab (triplet), encorafenib and cetuximab (doublet), or investigator's choice of irinotecan-based chemotherapy with cetuximab.
Median overall survival was 9.0 months with the triplet and 8.4 months with the doublet against 5.4 months with control; response rates were 26 and 20 percent against 2 percent. The MEK inhibitor added little, so the doublet was approved.
- Median overall survival 9.0 (triplet) and 8.4 (doublet) vs 5.4 months (control).
- Objective response 26 percent, 20 percent and 2 percent.
Encorafenib-cetuximab became the standard second-line treatment for BRAF V600E colorectal cancer, and BREAKWATER has since moved the combination, with chemotherapy, into first line.
- Responses are short-lived compared with BRAF-targeted therapy in melanoma.
- Control arm chemotherapy performed poorly.
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