Binimetinib

DAE Class; Rx

Common Brand Names; Mektovi

• Antineoplastics, MEK Inhibitors

MEK inhibitor
Used for unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with encorafenib
Cardiomyopathy, venous thromboembolism, interstitial lung disease, and rhabdomyolysis have been reported

Indicated in combination with encorafenib for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test

Indicated in combination with encorafenib for patients with unresectable or metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test

None

All grades of severity are listed unless otherwise indicated

>10%

Increased creatinine (93%)

Increased creatine phosphokinase (58%)

Increased gamma glutamyl transferase (GGT) (45%)

Fatigue (43%)

Nausea (41%)

Diarrhea (36%)

Anemia (36%)

Vomiting (30%)

Increased AST/ALT (27-29%)

Abdominal pain (28%)

Constipation (22%)

Rash (22%)

Increased alkaline phosphatase (21%)

Visual impairment (20%)

Serous retinopathy/retinal pigment epithelial dystrophy (RPED) (20%)

Hemorrhage (19%)

Hyponatremia (18%)

Pyrexia (18%)

Dizziness (15%)

Leukopenia (13%)

Lymphopenia (13%)

Neutropenia (13%)

Peripheral edema (13%)

Increased GGT, Grades 3 and 4 (11%)

Hypertension (11%)

In the COLUMBUS trial, venous thromboembolism (VTE) occurred in 6% of patients receiving binimetinib in combination with encorafenib, including 3.1% of patients who developed pulmonary embolism

In patients with BRAF mutation-positive melanoma receiving binimetinib with encorafenib (n=690), 2 patients (0.3%) developed interstitial lung disease (ILD), including pneumonitis; assess new or progressive unexplained pulmonary symptoms or findings for possible ILD

Hepatotoxicity can occur when binimetinib concomitantly used with encorafenib; monitor liver laboratory tests before initiating, monthly during treatment, and as clinically indicated

Rhabdomyolysis can occur when binimetinib is administered in combination with encorafenib; monitor CPK and creatinine levels prior to initiating treatment, periodically during treatment, and as clinically indicated; withhold, reduce dose, or permanently discontinue based on severity of adverse reaction

Hemorrhage can occur when encorafenib is administered in combination with binimetinib; hemorrhagic events include GI, hemorrhoidal, rectal, and intracranial hemorrhage, and hematochezia; withhold, reduce dose, or discontinue drug (see Dosage Modifications)

Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman (see Pregnancy)

Risks associated with combination treatment; refer to the encorafenib prescribing information for additional risk information

Pregnancy

Based on animal reproduction studies and its mechanism of action, fetal harm may occur when binimetinib is administered to a pregnant woman

There are no available clinical data on the use of binimetinib during pregnancy

Advise pregnant women of the potential risk to a fetus

Lactation

There are no data on the presence of binimetinib or its active metabolite in human milk, the effects of binimetinib on the breastfed infant, or on milk production

Because of the potential for serous adverse reactions from binimetinib in breastfed infants, advise women not to breastfeed during treatment with binimetinib and for 3 days after the final dose

Adults

90 mg/day PO.

Geriatric

90 mg/day PO.

Adolescents

Safety and efficacy not established.

Children

Safety and efficacy not established.

Infants

Safety and efficacy not established.

Binimetinib