|Drug class||BRAF kinase inhibitor|
|Main uses||Melanoma, colorectal cancer|
|Side effects||Tiredness, nausea, diarrhea,, abdominal pain, rash, joint pain|
|Typical dose||300 to 450 mg OD|
|Chemical and physical data|
|Molar mass||540.01 g·mol−1|
|3D model (JSmol)|
Encorafenib, sold under the brand name Braftovi, is a medication used to treat melanoma and colorectal cancer. Specifically it is used for cases which are BRAF V600E or V600K mutation-positive that cannot be removed by surgery. It is taken by mouth.
Common side effects include tiredness, nausea, diarrhea,, abdominal pain, rash, and joint pain. Other side effects may include bleeding, uveitis, QT prolongation, and other cancers. In those with minor liver problems a lower dose should be used. Use in pregnancy may harm the baby. It is a kinase inhibitor that blocks the BRAF protein.
Encorafenib was approved for medical use in the United States and Europe in 2018. In the United Kingdom for 4 weeks it costs the NHS about £5,600 as of 2021. In the United States this amount costs about 12,400 USD.
Treatment is continued as long as it is working.
Encorafenib acts as an ATP-competitive RAF kinase inhibitor, decreasing ERK phosphorylation and down-regulation of CyclinD1. This arrests the cell cycle in G1 phase, inducing senescence without apoptosis. Therefore, it is only effective in melanomas with a BRAF mutation, which make up 50% of all melanomas. The plasma elimination half-life of encorafenib is approximately 6 hours, occurring mainly through metabolism via cytochrome P450 enzymes.
Approval of encorafenib in the United States was based on a randomized, active-controlled, open-label, multicenter trial (COLUMBUS; NCT01909453) in 577 patients with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. People were randomized (1:1:1) to receive binimetinib 45 mg twice daily plus encorafenib 450 mg once daily, encorafenib 300 mg once daily, or vemurafenib 960 mg twice daily. Treatment continued until disease progression or unacceptable toxicity.
The major efficacy measure was progression-free survival (PFS) using RECIST 1.1 response criteria and assessed by blinded independent central review. The median PFS was 14.9 months for patients receiving binimetinib plus encorafenib, and 7.3 months for the vemurafenib monotherapy arm (hazard ratio 0.54, 95% CI: 0.41, 0.71, p<0.0001). The trial was conducted at 162 sites in Europe, North America and various countries around the world.
Several trials of LGX818, either alone or in combinations with the MEK inhibitor MEK162, are being run. As a result of a successful Phase Ib/II trials, Phase III trials are currently being initiated.
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