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Encorafenib, sold under the brand name Braftovi, is an anti-cancer medication used for the treatment of certain melanoma cancers. It is a small molecule BRAF inhibitor that targets key enzymes in the MAPK signaling pathway. This pathway occurs in many different cancers including melanoma and colorectal cancers.
The most common (≥25%) adverse reactions include fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia.
Encorafenib was developed by Novartis and Array BioPharma. In June 2018, it was approved by the FDA in combination with binimetinib for the treatment of people with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.
Encorafenib is not indicated for treatment of people with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC.
In December 2024, the FDA granted accelerated approval to encorafenib with cetuximab and FOLFOX (fluorouracil, leucovorin, and oxaliplatin) for people with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-approved test.
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 participants 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.
Efficacy for encorafenib with cetuximab and mFOLFOX6 was evaluated in BREAKWATER (NCT04607421), an active-controlled, open-label, multicenter trial. Participants were required to have treatment naïve BRAF V600E mutation-positive metastatic colorectal cancer, detected by the Qiagen BRAF V600E RGQ polymerase chain reaction kit. Participants were initially randomized 1:1:1 to one of the following treatment arms: encorafenib orally once daily with cetuximab IV infusion every 2 weeks (encorafenib+cetuximab arm); encorafenib orally once daily with cetuximab IV infusion every 2 weeks and mFOLFOX6 every 2 weeks (encorafenib+cetuximab+mFOLFOX6 arm); or FOLFOX, FOLFOXIRI (both every 2 weeks) or CAPOX (every 3 weeks)-each with or without bevacizumab (control arm). The trial was subsequently amended to limit randomization (1:1) to the encorafenib +cetuximab+mFOLFOX6 arm and the control arm. Treatment in all arms continued until disease progression, unacceptable toxicity, consent withdrawal, lost to follow-up, or death. The results of the encorafenib + cetuximab + mFOLFOX6 arm compared to the control arm served as the basis of this accelerated approval and are described below.
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