Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer
- Study type
- Clinical trial
- Study name
- BEACON CRC
- Phase
- Phase 3
- Design
- Open-label, three-arm randomised trial (1:1:1 ratio); results of a prespecified interim analysis are reported
- Sample size
- 665 patients
- Source
- N Engl J Med · 2019
- Trial registration
- NCT02928224
In plain words
In this study, people with advanced bowel cancer that had a particular genetic change called BRAF V600E, and whose earlier treatments had stopped working, received one of three treatments. The combination of encorafenib, binimetinib and cetuximab helped people live longer and shrank tumours better than chemotherapy with cetuximab. The two-drug combination of encorafenib and cetuximab also helped people live longer than the control treatment.
Key results
Treatment arms and regimens
Encorafenib 300 mg orally once daily + binimetinib orally twice daily (dose not stated in the available sources) + cetuximab IV 400 mg/m² as the first dose, then 250 mg/m² weekly; until disease progression or unacceptable toxicity. (This triplet combination is not approved for colorectal cancer.)
Encorafenib 300 mg orally once daily + cetuximab IV 400 mg/m² as the first dose, then 250 mg/m² weekly; until disease progression or unacceptable toxicity (the FDA-approved regimen after prior therapy).
Investigator's choice, with cetuximab at the same dose: irinotecan 180 mg/m² IV on days 1 and 15 of each 28-day cycle, or FOLFIRI on days 1 and 15 (irinotecan 180 mg/m², folinic acid 400 mg/m², fluorouracil 400 mg/m² bolus, then a 2-day continuous infusion); until disease progression or unacceptable toxicity.
Source of the regimen details: FDA label for encorafenib (BRAFTOVI; Clinical Studies section, BEACON CRC) and ClinicalTrials.gov NCT02928224; the binimetinib dose is not stated in these sources
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with BRAF V600E-mutated metastatic colorectal cancer whose disease had progressed after one or two previous regimens.
Endpoints
Primary endpoints: overall survival and objective response rate in the triplet group compared with the control group. Secondary endpoint: overall survival in the doublet group compared with the control group.
Safety and side effects
Grade 3 or higher adverse events occurred in 58% of patients in the triplet group, 50% in the doublet group and 61% in the control group.
Clinical significance and place in guidelines
This trial showed that combined targeted therapy improves overall survival and response rate over standard therapy in previously treated BRAF V600E-mutated metastatic colorectal cancer, and it underlines the need to test for the BRAF V600E mutation. The status of drug approvals and guideline recommendations should be checked separately; the abstract does not address them.
Limitations
The results come from a prespecified interim analysis. The trial was open-label. Patients were enrolled after one or two previous regimens, and the findings are limited to this population.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.