Binimetinib (Mektovi) Treatment Guide: Uses, Side Effects, Dosage, and What to Expect

In June 2018, the U.S. Food and Drug Administration (FDA) approved Binimetinib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations. In October 2023, the FDA approved Binimetinib in combination with Encorafenib for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring a BRAF V600E mutation.

Indications for Binimetinib

Melanoma

Binimetinib is indicated, in combination with Encorafenib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation (FDA granted Orphan Drug designation for this use).

Prior to treatment initiation, the presence of a BRAF V600E or V600K mutation in tumor specimens must be confirmed using an FDA-approved diagnostic test.

Non-Small Cell Lung Cancer

Binimetinib, in combination with Encorafenib, is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring a BRAF V600E mutation.

Prior to treatment initiation, the presence of a BRAF V600E mutation in tumor or plasma specimens must be confirmed using an FDA-approved diagnostic test. If the mutation is not detected in a plasma specimen, tumor tissue should be tested.

Monitoring Recommendations for Binimetinib

Assess left ventricular ejection fraction (LVEF) by echocardiogram or MUGA scan one month after initiating Binimetinib, then every 2 to 3 months thereafter during treatment.

Evaluate for visual symptoms at each visit. Perform periodic ophthalmic examinations to monitor for new or worsening visual disturbances and to follow new or persistent ophthalmic abnormalities.

Assess patients for new or progressive unexplained pulmonary symptoms or signs to rule out possible interstitial lung disease (ILD).

Monitor liver function tests monthly during treatment and as clinically indicated.

Monitor creatine phosphokinase (CPK) and creatinine levels regularly during treatment and as clinically indicated.

Monitor for signs of bleeding and for thromboembolism during treatment.

Monitor patients for new malignancies during treatment and after discontinuation.

Dosage and Administration for Binimetinib

Administration Method

Oral administration: Take orally twice daily, approximately 12 hours apart, with or without food.

Recommended Dosage

(1) Adult Melanoma

The recommended dosage is 45 mg orally twice daily in combination with Encorafenib. Continue treatment until disease progression or unacceptable toxicity occurs.

If Encorafenib is permanently discontinued, Lucius Pharmaceuticals Binimetinib should also be discontinued. Refer to the Encorafenib prescribing information for dose adjustment information for Encorafenib.

(2) Non-Small Cell Lung Cancer (NSCLC)

The recommended dosage is 45 mg orally twice daily in combination with Encorafenib. Continue treatment until disease progression or unacceptable toxicity occurs.

If Encorafenib is permanently discontinued, Binimetinib should also be discontinued. Refer to the Encorafenib prescribing information for dose adjustment information for Encorafenib.

Common Adverse Reactions to Binimetinib

Common adverse reactions (≥25%) occurring in patients treated with Binimetinib in combination with Encorafenib for melanoma and non-small cell lung cancer:

Melanoma

Fatigue, nausea, diarrhea, vomiting, abdominal pain.

Non-Small Cell Lung Cancer

Fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, cough.

Warnings and Precautions for Binimetinib

Combination Therapy

When Binimetinib is used in combination with Encorafenib, consider the warnings, precautions, and contraindications for Encorafenib.

New Primary Malignancies

New primary malignancies, both cutaneous and non-cutaneous, can occur. Monitor patients for new malignancies before starting treatment, during treatment, and after discontinuation.

Cardiomyopathy

Cardiomyopathy (manifesting as symptomatic or asymptomatic left ventricular dysfunction) has been reported in patients receiving Binimetinib in combination with Encorafenib, sometimes requiring temporary interruption or dose reduction. Left ventricular dysfunction may require treatment interruption, subsequent dose reduction, or discontinuation.

Venous Thromboembolism

Venous thromboembolism (VTE) has been reported in patients receiving Binimetinib in combination with Encorafenib. Deep venous thrombosis or pulmonary embolism may require treatment interruption, subsequent dose reduction, or discontinuation.

Ocular Effects

Ocular toxicities, including serous retinopathy, retinal vein occlusion, retinal pigment epithelial detachment, and macular edema, have been reported in patients receiving Binimetinib in combination with Encorafenib. Monitor patients for visual symptoms at each visit. Ocular toxicity may require treatment interruption, dose reduction, or permanent discontinuation.

Pulmonary Effects

Interstitial lung disease or pneumonitis has been reported in patients receiving Binimetinib in combination with Encorafenib. Evaluate patients presenting with manifestations of ILD (e.g., new or progressive pulmonary symptoms). Interstitial lung disease may require treatment interruption, subsequent dose reduction, or discontinuation.

Hepatotoxicity

Liver function test abnormalities (i.e., elevated ALT, AST, or alkaline phosphatase) have been reported in patients receiving Binimetinib in combination with Encorafenib.

Monitor liver function tests before treatment, monthly during treatment, and more frequently as clinically indicated. Liver function test abnormalities may require treatment interruption, dose reduction, or permanent discontinuation.

Musculoskeletal Effects

Rhabdomyolysis has been reported in patients receiving Binimetinib in combination with Encorafenib. Elevated CPK levels may require treatment interruption, subsequent dose reduction, or discontinuation.

Hemorrhage

Hemorrhage has been reported in patients receiving Binimetinib in combination with Encorafenib. Fatal intracranial hemorrhages have also been reported. Hemorrhagic events may require treatment interruption, subsequent dose reduction, or discontinuation.

Fetal/Neonatal Morbidity and Mortality

Binimetinib can cause fetal harm. Embryotoxicity, fetotoxicity, and teratogenicity have been demonstrated in animals. Verify pregnancy status before starting treatment. Avoid pregnancy during treatment. Females of reproductive potential should use effective contraception during treatment with Binimetinib and for at least 30 days after the final dose.

Use in Specific Populations for Binimetinib

Pregnancy

Binimetinib can cause fetal harm.

Lactation

It is unknown whether Binimetinib or its metabolites are present in human milk. Effects on the breastfed infant and on milk production are also unknown. Breastfeeding should be discontinued during treatment and for 3 days after the final dose.

Females and Males of Reproductive Potential

Verify pregnancy status in females of reproductive potential before starting treatment.

Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after the final dose of Binimetinib.

Pediatric Use

Safety and effectiveness have not been established.

Geriatric Use

No overall differences in the safety or effectiveness of Binimetinib in combination with Encorafenib were observed between elderly patients and younger adults.

Hepatic Impairment

Mild hepatic impairment does not significantly affect the systemic exposure of Binimetinib; no dose adjustment is required.

Systemic exposure is increased in patients with moderate or severe hepatic impairment; dose reduction is recommended.

Renal Impairment

Severe renal impairment does not significantly affect the systemic exposure of Binimetinib.

Drug Interactions with Binimetinib

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP3A4 Substrates

No pharmacokinetic interactions have been observed to date.

Drugs Affecting Uridine Diphosphate Glucuronosyltransferase Enzymes

(1) UGT1A1 Inhibitors

No clinically meaningful pharmacokinetic interactions are expected.

(2) UGT1A1 Inducers

No clinically meaningful pharmacokinetic interactions are expected.

Drugs Transported by Organic Cation Transporters

OCT1 or OCT2 Substrates

No clinically meaningful pharmacokinetic interactions are expected.

Specific Drugs

Atazanavir, Encorafenib, Midazolam, Rabeprazole, among others, did not significantly affect the systemic exposure of Binimetinib.