BEACON CRC (triplet regimen)
Trial question
What is the role of a combination of encorafenib, binimetinib, and cetuximab in patients with metastatic CRC with BRAF V600E mutation?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
55.0% female
45.0% male
N = 445
445 patients (246 female, 199 male).
Inclusion criteria: patients with BRAF V600E-mutated metastatic CRC who had disease progression after 1 or 2 previous regimens.
Key exclusion criteria: prior treatment with any RAF inhibitor, MEK inhibitor, or other EGFR inhibitors; symptomatic brain metastasis or leptomeningeal disease; acute or chronic pancreatitis; uncontrolled BP despite medical treatment.
Interventions
N=224 triplet regimen (combination of encorafenib 300 mg daily, binimetinib 45 mg BID, and cetuximab 250-400 mg/m² weekly).
N=221 control (investigators choice of either cetuximab and irinotecan or cetuximab and folinic acid, fluorouracil, and irinotecan).
Primary outcome
Median overall survival
9 months
5.4 months
9.0 months
6.8 months
4.5 months
2.3 months
0.0 months
Triplet
regimen
Control
Significant
increase ▲
Significant increase in median overall survival (9 months vs. 5.4 months; HR 1.92, 95% CI 1.43 to 2.56).
Secondary outcomes
Significant increase in objective response rate (26% vs. 2%; AD 24%, 95% CI 9.76 to 38.24).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with BRAF V600E-mutated metastatic CRC who had disease progression after 1 or 2 previous regimens, triplet regimen were superior to control with respect to median overall survival.
Reference
Scott Kopetz, Axel Grothey, Rona Yaeger et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643.
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