Braftovi (Encorafenib): Uses, Side Effects & Warnings

Key Takeaways

• Braftovi (encorafenib) is a BRAF kinase inhibitor used to treat BRAF V600E- or V600K-mutant melanoma and BRAF V600E-mutant colorectal cancer.
• It is most commonly prescribed alongside binimetinib (for melanoma) or cetuximab (for colorectal cancer).
• Common side effects include fatigue, nausea, joint pain, and skin reactions.
• Serious risks include new primary malignancies, hemorrhage, and cardiac dysfunction, requiring regular monitoring.
• Patients should inform their oncologist of all medications, including supplements, before starting treatment.

What Is Braftovi (Encorafenib) Used For in Cancer Treatment

Encorafenib is a small-molecule BRAF kinase inhibitor that works by blocking the activity of mutated BRAF proteins, which would otherwise drive uncontrolled cancer cell growth. Approximately 50% of melanomas and a smaller but significant proportion of colorectal cancers carry a BRAF V600E or V600K mutation, according to published oncology literature, making these mutations important therapeutic targets. By inhibiting this overactive signaling pathway, encorafenib helps slow or stop tumor progression.

The FDA has approved encorafenib for two primary indications. First, it is indicated—in combination with binimetinib—for adults with unresectable or metastatic melanoma harboring a BRAF V600E or V600K mutation as detected by an FDA-approved test. Second, it is approved in combination with cetuximab for adults with metastatic colorectal cancer (mCRC) whose tumors carry the BRAF V600E mutation and who have received prior systemic therapy. These combination regimens are designed to provide more complete and durable tumor suppression than single-agent BRAF inhibition alone.

Before encorafenib is prescribed, tumor testing is mandatory to confirm the presence of a relevant BRAF mutation. Patients without these specific mutations should not receive this therapy, as the drug is unlikely to be effective and may cause unnecessary harm. Oncologists use validated companion diagnostic assays to guide this decision, ensuring the treatment is matched appropriately to each patient’s tumor biology.

Braftovi (Encorafenib) Dosage and How It Is Administered

Encorafenib is available as oral capsules and is taken once daily, with or without food. For patients with unresectable or metastatic melanoma, the recommended dose is 450 mg once daily when used in combination with binimetinib. For patients with metastatic colorectal cancer, the recommended dose is 300 mg once daily when used in combination with cetuximab. These dosing regimens reflect clinical trial data supporting both efficacy and manageable tolerability.

Patients should swallow the capsules whole and take each dose at approximately the same time each day. If a dose is missed and it is within 12 hours of the scheduled time, the missed dose may be taken; if more than 12 hours have elapsed, the dose should be skipped and the next scheduled dose taken as usual. Capsules should never be crushed, opened, or dissolved, as this may alter drug absorption and increase the risk of adverse effects.

Dose modifications—including temporary interruptions or permanent discontinuation—may be required based on the severity of side effects or changes in a patient’s clinical status. Healthcare providers follow established dose-reduction guidelines for events such as hepatotoxicity, uveitis, or cutaneous toxicity. Patients should never adjust their own dose without guidance from their oncologist, as doing so could compromise treatment effectiveness or worsen safety risks.

Common and Serious Side Effects of Encorafenib

Like all targeted cancer therapies, encorafenib is associated with a range of side effects that vary in frequency and severity. Knowing what to expect helps patients report symptoms promptly and enables their care team to intervene before complications escalate. Side effects may differ depending on whether encorafenib is combined with binimetinib or cetuximab.

The most frequently reported side effects observed in clinical trials include fatigue, nausea, diarrhea, vomiting, abdominal pain, arthralgia (joint pain), and skin reactions such as palmar-plantar erythrodysesthesia (hand-foot syndrome). Headache, peripheral neuropathy, and changes in liver enzyme levels are also commonly documented. While many of these effects are manageable with supportive care or dose adjustment, patients should report any new or worsening symptoms to their healthcare provider promptly.

Serious adverse reactions require particular attention. The following events have been identified as clinically significant risks associated with encorafenib treatment:

• New primary malignancies: Cutaneous squamous cell carcinoma and other skin cancers can develop; regular dermatologic monitoring is essential.
• Hemorrhage: Major bleeding events, including intracranial and gastrointestinal hemorrhage, have been reported and may be life-threatening.
• Uveitis and iritis: Ocular inflammation can cause vision changes and requires prompt ophthalmologic evaluation.
• Cardiomyopathy: Decreased left ventricular ejection fraction (LVEF) has been observed; baseline and periodic cardiac assessments are recommended.
• Hepatotoxicity: Elevations in liver enzymes may occur, necessitating regular liver function monitoring.
• QTc interval prolongation: Encorafenib can affect cardiac electrical activity, posing a risk for serious arrhythmias.

Patients experiencing sudden vision changes, unusual bleeding, severe abdominal pain, or chest discomfort should seek immediate medical attention. Early identification and management of these serious events can prevent permanent harm and allow treatment to continue safely.

Encorafenib Warnings, Precautions, and What Patients Should Know Before Taking

The FDA-approved prescribing information for encorafenib includes several important warnings that patients and clinicians must review before initiating therapy. These precautions are based on clinical trial safety data and post-marketing reports, reflecting real-world risks associated with this drug. Adherence to monitoring schedules and open communication with the treating oncologist are central to minimizing harm.

Embryo-fetal toxicity is a critical warning: encorafenib can cause fetal harm when administered to a pregnant person. Women of reproductive potential should use effective contraception during treatment and for at least 2 weeks after the final dose. Male patients with female partners of reproductive potential should also use contraception during therapy. Breastfeeding is not recommended during treatment or for 2 weeks after the last dose, as the potential risk to a nursing infant cannot be excluded.

Drug interactions represent another significant concern. Encorafenib is a strong inhibitor of CYP3A4 and can increase plasma concentrations of medications metabolized by this enzyme, potentially causing toxicity. Conversely, strong CYP3A4 inducers can reduce encorafenib levels and diminish its effectiveness. Patients should provide a complete list of all prescription medications, over-the-counter drugs, vitamins, and herbal supplements to their oncologist before starting treatment. Grapefruit and grapefruit juice should also be avoided, as they may interfere with drug metabolism.

Baseline evaluations before starting encorafenib should include an electrocardiogram (ECG) to assess QTc interval, liver function tests, and an ophthalmologic examination if the patient has a history of eye conditions. Cardiac function assessment via echocardiogram or multigated acquisition (MUGA) scan is also advisable given the risk of cardiomyopathy. These tests should be repeated at regular intervals throughout treatment to detect any emerging abnormalities early.

Patients with moderate or severe hepatic impairment require dose adjustment or may not be appropriate candidates for encorafenib therapy. Similarly, patients with baseline QTc prolongation or those taking QT-prolonging medications need careful risk-benefit evaluation before initiating treatment. Any significant comorbidity should be discussed with the oncology team to determine whether encorafenib is suitable and at what dose.

Frequently Asked Questions

Can encorafenib be taken as a standalone treatment?

Encorafenib is not typically used as a single agent in approved treatment settings. For BRAF V600E/V600K-mutant melanoma, it is used alongside binimetinib. For BRAF V600E-mutant metastatic colorectal cancer, it is paired with cetuximab. These combinations are designed to delay resistance and improve outcomes. Using encorafenib alone may increase the risk of resistance developing more quickly and is generally not recommended outside of specific clinical trial protocols.

How long do patients usually take encorafenib?

Treatment duration with encorafenib is typically continued until disease progression or unacceptable toxicity occurs. There is no fixed treatment course; the duration is individualized based on how each patient responds and tolerates the medication. Some patients remain on therapy for months to years if the cancer remains controlled. Regular imaging and clinical assessments help the oncology team evaluate ongoing response and determine whether treatment should continue, be adjusted, or be discontinued.

Is encorafenib safe for older adults?

Clinical trials included patients aged 65 and older, and no overall differences in safety or efficacy were observed compared to younger patients. However, older adults may have a higher burden of comorbidities and may be taking multiple medications that could interact with encorafenib. Close monitoring is especially important in this population. Dose adjustments may be needed based on renal or hepatic function, and oncologists should conduct a thorough review of each older patient’s overall health profile before initiating therapy.