Encorafenib (Braftovi) is a kinase inhibitor targeting BRAFV600E or V600K mutations, indicated for the treatment of specific types of melanoma, colorectal cancer, and non-small cell lung cancer. While this drug can effectively inhibit tumor growth, it may be associated with a range of adverse reactions, some of which can be severe.

Adverse Reactions of Encorafenib (Braftovi)

Common Adverse Reactions

Melanoma (in combination with binimetinib): Fatigue, nausea, vomiting, abdominal pain, arthralgia.

Colorectal cancer (in combination with cetuximab and mFOLFOX6): Peripheral neuropathy, nausea, fatigue, rash, diarrhea, decreased appetite, vomiting, hemorrhage, abdominal pain, pyrexia.

Colorectal cancer (in combination with cetuximab): Fatigue, nausea, diarrhea, acneiform dermatitis, abdominal pain, decreased appetite, arthralgia, rash.

Non-small cell lung cancer (in combination with binimetinib): Fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual disturbances, constipation, dyspnea, rash, cough.

Severe Adverse Reactions

New Primary Malignancies

Encorafenib may increase the risk of cutaneous malignancies such as cutaneous squamous cell carcinoma and basal cell carcinoma, and may also promote the development of non-cutaneous malignancies (e.g., RAS mutation-associated tumors).

Regular dermatological examinations are recommended before treatment, every 2 months during treatment, and within 6 months after discontinuation. Suspicious lesions should be resected and subjected to pathological evaluation.

Permanent discontinuation of encorafenib is required if non-cutaneous malignancies occur.

Cardiomyopathy

Concomitant use with binimetinib may cause left ventricular dysfunction, manifested as decreased ejection fraction.

Cardiac function monitoring via echocardiography or MUGA scan should be performed before treatment, 1 month after treatment initiation, and every 2–3 months thereafter.

Dose adjustment or treatment interruption is necessary if symptomatic heart failure or a significant decrease in ejection fraction occurs.

Hepatotoxicity

Combination therapy may lead to elevated liver enzymes. Liver function parameters should be monitored before treatment, monthly, and as clinically indicated.

Treatment interruption or dose adjustment is required in case of severe liver injury.

Hemorrhage

Severe bleeding events include gastrointestinal hemorrhage, intracranial hemorrhage, and other potentially fatal bleeding complications.

Patients should seek immediate medical attention if they experience signs of abnormal bleeding (e.g., epistaxis, hematochezia, headache, hematemesis).

Important Precautions for Encorafenib (Braftovi)

Genetic Testing Prior to Administration

The presence of BRAFV600E or V600K mutations in the tumor must be confirmed using an FDA-approved testing method before treatment initiation.

This drug is not indicated for patients with wild-type BRAF tumors, as it may potentially promote tumor growth.

Principles for Dose Adjustment and Discontinuation

If binimetinib (used in combination) is interrupted or discontinued, the dose of encorafenib should be reduced accordingly.

Encorafenib should be discontinued if cetuximab (used in combination) is withdrawn.

Dose reduction, interruption, or permanent discontinuation should be implemented in accordance with clinical guidelines based on the severity of adverse reactions.

Drug Interactions

Avoid concomitant use with strong or moderate CYP3A4 inhibitors (e.g., certain antifungal agents, grapefruit products). If coadministration is unavoidable, dose adjustment of encorafenib is required.

Avoid concomitant use with strong CYP3A4 inducers, as this may reduce the efficacy of encorafenib.

Encorafenib is a strong CYP3A4 inducer, which may decrease the plasma concentrations of certain drugs, including hormonal contraceptives.

When used concomitantly with substrates of OATP1B1, OATP1B3, or BCRP, close monitoring for toxic reactions of the latter drugs is recommended.