# BEACON CRC: encorafenib and cetuximab with or without binimetinib in BRAF V600E-mutated colorectal cancer

Source: https://onco.cc/key-papers/paper-beacon-crc-kopetz-nejm-2019/  
OnCo record `paper-beacon-crc-kopetz-nejm-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2019
- DOI: 10.1056/NEJMoa1908075
- Authors: Kopetz S, Grothey A, Yaeger R, et al.
- Findings: Median overall survival 9.0 (triplet) and 8.4 (doublet) vs 5.4 months (control).; Objective response 26 percent, 20 percent and 2 percent.
- What it means: 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.
- Caveats: Responses are short-lived compared with BRAF-targeted therapy in melanoma.; Control arm chemotherapy performed poorly.

## Sources

- N Engl J Med 2019: https://doi.org/10.1056/NEJMoa1908075
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31566309/

## Connected records

- cancers: [BRAF V600E-mutant colorectal cancer](https://onco.cc/cancers/braf-v600e-colorectal/)
- drugs: [Binimetinib](https://onco.cc/drugs/binimetinib/), [Cetuximab](https://onco.cc/drugs/cetuximab/), [Encorafenib](https://onco.cc/drugs/encorafenib/)
- trials: [BEACON CRC](https://onco.cc/trials/beacon-crc/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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