Trametinib (Mekinist) is a targeted therapy drug that demonstrates significant efficacy in the treatment of BRAFV600E or V600K mutation-positive melanoma, but the associated adverse reactions require close attention.
Adverse Reactions of Trametinib (Mekinist)
Common Adverse Reactions
Skin and subcutaneous tissue disorders are the most frequent, with rash occurring in 57% of patients, 8% of which are of grade 3–4 severity.
Other cutaneous reactions include acneiform dermatitis (19%), xeroderma (11%), pruritus (10%), and paronychia (10%).
Gastrointestinal system disorders: Diarrhea (mostly mild to moderate) affects 43% of patients, stomatitis in 15%, and abdominal pain in 13%.
Laboratory abnormalities: Elevated aspartate aminotransferase (AST) is observed in 60% of patients, elevated alanine aminotransferase (ALT) in 39%, hypoalbuminemia in 42%, and anemia in 38%.
Lymphoedema is detected in 32% of patients, hypertension in 15%, and hemorrhagic manifestations in 13%.
Severe Adverse Reactions
Cardiomyopathy
In pivotal clinical trials, 7% of patients treated with trametinib developed cardiomyopathy (including heart failure, left ventricular dysfunction, or decreased left ventricular ejection fraction [LVEF]), among whom 5% required permanent treatment discontinuation.
11% of patients experienced LVEF below the lower limit of normal with an absolute decrease of ≥10% from baseline, and 5% of these patients had an LVEF reduction of ≥20%.
Current guidelines mandate LVEF assessment via echocardiography or MUGA scan prior to treatment initiation, 1 month after treatment start, and then every 2–3 months thereafter.
Treatment should be interrupted if LVEF shows an absolute decrease of ≥10% from baseline and falls below the lower limit of normal. Permanent discontinuation is required in cases of symptomatic cardiomyopathy or persistent asymptomatic LVEF abnormalities without improvement within 4 weeks.
Ocular Toxicity
Retinal pigment epithelial detachment (RPED) occurs in 0.8% of patients, characterized by bilateral multifocal macular lesions that may lead to visual impairment.
Retinal vein occlusion (RVO) has an incidence of 0.2%, which can cause macular edema, visual loss, neovascularization, and glaucoma.
Guidelines recommend immediate ophthalmologic evaluation for patients with new-onset visual disturbances. Treatment should be withheld upon confirmation of RPED; permanent discontinuation is indicated if no improvement is seen within 3 weeks. For RVO, immediate and permanent treatment discontinuation is required.
Pulmonary Complications
Interstitial lung disease (ILD) or pneumonia occurs in 1.8% of patients, some of whom require hospitalization.
Treatment should be suspended in patients with new or progressive pulmonary symptoms (such as cough, dyspnea, hypoxia, pleural effusion, or infiltrates on imaging). Permanent discontinuation is necessary if treatment-related ILD is confirmed.
Precautions for Trametinib (Mekinist) Administration
Special Population Warnings
Pregnancy: Trametinib exhibits embryotoxicity. Women of childbearing potential must use highly effective contraceptive measures during treatment and for 4 months after discontinuing the drug.
Lactation: Breastfeeding is not recommended during treatment; either discontinue breastfeeding or stop the drug.
Dosing Specifications and Monitoring
Tumor mutation confirmation: The presence of BRAFV600E or V600K mutations must be verified using an FDA-approved diagnostic assay before treatment initiation.
Recommended dosage: 2 mg once daily, to be taken 1 hour before or 2 hours after a meal. If a dose is missed, the next dose should be taken at least 12 hours later.
Systematic multi-organ monitoring is required, including regular cardiac function assessment, ophthalmologic examinations, monitoring of cutaneous toxicity, blood pressure measurement, and liver function follow-up.
