June 27, 2018—Today, the U.S. Food and Drug Administration (FDA) approved the use of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib for the treatment of patients with metastatic or otherwise unresectable melanoma harboring a BRAF V600E/K mutation. This marks the third BRAF/MEK inhibitor combination therapy approved for advanced melanoma.
Today’s approval was based on the randomized, open-label, three-armed phase III COLUMBUS trial (NCT01909453) in which 577 patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma were randomized 1:1:1 to receive encorafenib in combination with binimetinib (n=192), encorafenib alone (n=194), or vemurafenib, another BRAF inhibitor (n=191).
The median progression-free survival (PFS) was 14.9 months, 9.6 months, and 7.3 months for the novel combination, encorafenib monotherapy, and vemurafenib monotherapy arms, respectively. The median overall survival (OS) for patients receiving the approved combination was 33.6 months compared with 23.5 months for patients receiving encorafenib alone, and 16.9 months for patients receiving vemurafenib monotherapy.
In the COLUMBUS trial, 34% of patients in the combination group experienced serious adverse events (AEs). In the encorafenib-monotherapy group, 34% of patients experienced a serious AE; in the vemurafenib control group, 37% did. In the combination group, the most common grade 3-4 AEs included increased gamma-glutamyltransferase (9%), increased creatine phosphokinase (7%), and hypertension (6%); in the encorafenib-monotherapy group, grade 3-4 AEs included hand-foot syndrome (14%), muscle pain (10%), and joint pain (9%). Other common AEs (≥25%) observed in patients receiving the combination included fatigue, nausea, diarrhea, vomiting, abdominal pain, and joint pain. Treatment discontinuation due to AE occurred in 5% of patients receiving the combination.
The BRAF/MEK inhibitor combinations dabrafenib/trametinib and vemurafenib/cobimetinib are also approved in this treatment setting.
Prescribing information for encorafenib can be found here. Prescribing information for binimetinib can be found here.
Jonathan A. Bell
Published Online: Wednesday, June 27, 2018
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Third BRAF/MEK inhibitor approved for the treatment of advanced melanoma
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