Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer.
By S. Kopetz, A. Grothey, R. Yaeger, E. Van Cutsem, J. Desai, T. Yoshino, H. Wasan, Fortunato Ciardiello, F. Loupakis, Y. Hong and 25 more. New England Journal of Medicine, 2019
1,107 citations recorded by the source corpus.
BACKGROUND Patients with metastatic colorectal cancer with the BRAF V600E mutation have a poor prognosis, with a median overall survival of 4 to 6 months after failure of initial therapy. Inhibition of BRAF alone has limited activity because of pathway reactivation through epidermal growth factor receptor signaling. METHODS In this open-label, phase 3 trial, we enrolled 665 patients with BRAF V600E-mutated metastatic colorectal cancer who had had disease progression after one or two previous regimens. Patients were randomly assigned in a 1:1:1 ratio to receive encorafenib, binimetinib, and cetuximab (triplet-therapy group); encorafenib and cetuximab (doublet-therapy group); or the investigators' choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan) (control group). The primary end points were overall survival and objective response rate in the triplet-therapy group as compared with the control group. A secondary end point was overall survival in the doublet-therapy group as compared with the control group. We report here the results of a prespecified interim analysis. RESULTS The median overall survival was 9.0 months in the triplet-therapy group and 5.4 months in the control group (hazard ratio for death, 0.52; 95% confidence interval [CI], 0.39 to 0.70; P<0.001). The confirmed response rate was 26% (95% CI, 18 to 35) in the triplet-therapy group and 2% (95% CI, 0 to 7) in the control group (P<0.001). The median overall survival in the doublet-therapy group was 8.4 months (hazard ratio for death vs. control, 0.60; 95% CI, 0.45 to 0.79; P<0.001). Adverse events of grade 3 or higher occurred in 58% of patients in the triplet-therapy group, in 50% in the doublet-therapy group, and in 61% in the control group. CONCLUSIONS A combination of encorafenib, cetuximab, and binimetinib resulted in significantly longer overall survival and a higher response rate than standard therapy in patients with metastatic colorectal cancer with the BRAF V600E mutation. (Funded by Array BioPharma and others; BEACON CRC ClinicalTrials.gov number, NCT02928224; EudraCT number, 2015-005805-35.).
Subfields: Molecular Biology, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/ffb20682723dcd13b49af89a5ada6b116a8d98a0
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
In Oncology
Citations in the corpus
- Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: A report from the ESMO Precision Medicine Working Group. (2020, background): “The addition of encorafenib (a BRAF inhibitor) to cetuximab was associated with a significant survival benefit in a recent phase III trial in patients presenting a BRAF mutation.(82) Alterations in mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) can be identified by IHC and MSI-H by PCR to dete”