Braftovi is a targeted therapy specifically for BRAF V600E gene mutations. It is often used in combination with other drugs (such as cetuximab and bimetinib), offering new treatment hope to many patients.
Indications for Braftovi:
1. Melanoma
Braftovi, in combination with bimetinib, is used to treat unresectable or metastatic melanoma harboring BRAF V600E or V600K mutations (designated an orphan drug for this purpose by the FDA).
2. Colorectal Cancer
Braftovi, in combination with cetuximab, is used to treat previously treated adult patients with BRAF V600E mutations and metastatic colorectal cancer.
3. Non-Small Cell Lung Cancer
Braftovi (cannefenib) is used in combination with bimetinib to treat adult metastatic non-small cell lung cancer (NSCLC) with the BRAF V600E mutation (designated as an orphan drug for this purpose by the FDA).
Dosage and Administration of Braftovi (cannefenib)
1. Recommended Dosage
(1) Adult Dosage for Melanoma
450 mg orally once daily in combination with bimetinib. Continue treatment until disease progression or unacceptable toxicity.
(2) Adult Dosage for Colorectal Cancer
300 mg orally once daily in combination with cetuximab. Continue treatment until disease progression or unacceptable toxicity.
(3) Adult Dosage for Non-Small Cell Lung Cancer
450 mg orally once daily in combination with bimetinib. Continue treatment until disease progression or unacceptable toxicity.
2. Pre-treatment Screening
(1) Before starting Braftovi treatment, confirm the presence of BRAF V600E or V600K mutations using an FDA-approved diagnostic test, depending on the indication.
(2) Assess left ventricular ejection fraction (LVEF) by echocardiography or multigated angiography (MUGA).
(3) Monitor liver function.
(4) Perform skin assessment.
(5) Detect and correct hypokalemia or hypomagnesemia.
(6) Confirm pregnancy status in women of reproductive potential.
3. Patient Monitoring
(1) Assess LVEF by echocardiography or MUGA one month after starting Braftovi, and then every 2-3 months during treatment.
(2) Monitor liver function monthly during treatment, and monitor as needed based on clinical condition.
(3) Perform skin assessment every 2 months during treatment, and also within 6 months after discontinuation of combination therapy. Monitor for signs and symptoms of newly diagnosed non-cutaneous malignancies.
(4) Perform regular ophthalmological examinations, and conduct further examinations based on clinical findings if visual abnormalities occur.
(5) Monitor patients at risk of or with a prolonged (corrected) QT interval; correct hypokalemia or hypomagnesemia during treatment.
4. Administration
(1) Take Braftovi orally once daily, with or without food.
(2) If a dose is missed for more than 12 hours, skip the missed dose and take the next dose at the usual time.
(3) If vomiting occurs after administration, do not take the missed dose; take the next dose at the usual time.
Common Adverse Reactions of Braftovi
1. Common Adverse Reactions in Melanoma
Fatigue, nausea, vomiting, abdominal pain, arthralgia.
2. Common Adverse Reactions in Colorectal Cancer
Fatigue, nausea, diarrhea, acneiform dermatitis, abdominal pain, decreased appetite, arthralgia, rash.
3. Common Adverse Reactions in Non-Small Cell Lung Cancer
Fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual disturbances, constipation, dyspnea, rash, cough.
Precautions for Braftovi
1. Combination Therapy
When braftovi is used in combination with bimetinib or cetuximab, the precautions, precautions, and contraindications for bimetinib or cetuximab should be considered separately.
2. Newly Onset of Malignant Tumors
There have been reports of skin and non-skin malignant tumors. Monitor for signs and symptoms of newly onset of non-skin malignant tumors. If a newly onset of RAS-mutant positive non-skin malignant tumor occurs, permanently discontinue this drug.
3. Tumor Promotion in Wild-Type BRAF Melanoma
The presence of BRAF V600E or V600K mutations must be confirmed before initiating treatment.
4. Cardiomyopathy
Cardiomyopathy has been reported, which may manifest as a symptomatic or asymptomatic decrease in left ventricular ejection fraction (LVEF). Close monitoring is necessary during treatment in patients with pre-existing cardiovascular risk factors. If left ventricular dysfunction occurs, temporary interruption of treatment may be necessary, followed by a reduction in the dose of braftovi or discontinuation.
5. Hepatotoxicity
Abnormal liver function tests have been reported. Liver function tests should be performed before initiating braftovi treatment and monthly (or more frequently as clinically necessary) thereafter. If abnormal liver function tests occur during treatment, temporary interruption of treatment, a reduction in the dose, or discontinuation of braftovi may be necessary.
6. Bleeding
Bleeding events have been reported. If a bleeding event occurs, temporary interruption of treatment may be necessary, followed by a reduction in the dose or discontinuation.
7. Uveitis
Uveitis (including iritis and iridocyclitis) has been reported. Monitor patients for visual symptoms at each visit. If ocular toxicity occurs, temporary interruption of treatment, a reduction in the dose, or permanent discontinuation may be necessary.
8. QT Interval Prolongation
QT interval prolongation has been reported. If QT interval prolongation occurs, treatment may need to be interrupted, followed by dose reduction or discontinuation.
9. Fetal/Neonatal Morbidity and Death
May cause harm to the fetus. Confirm pregnancy status before starting treatment. Avoid pregnancy during treatment.
Special Populations for Braftovi Use
1. Pregnancy and Lactation
May cause harm to the fetus. It is unknown whether braftovi passes into human milk. The effects on breastfed infants and breast milk are also unknown. May reduce male fertility.
2. Pediatric Use
Safety and efficacy have not been established.
3. Elderly Patients
There is no overall difference in safety and efficacy between braftovi and younger adults when used in combination with bimetinib or cetuximab.
4. Hepatic Impairment
Mild hepatic impairment has no significant effect on the pharmacokinetics of braftovi and no dose adjustment is required. Studies have not been conducted in patients with moderate or severe hepatic impairment.
5. Renal Impairment
Mild or moderate renal impairment has no significant effect on systemic exposure to braftovi, and no dose adjustment is required. Studies have not been conducted in patients with severe renal impairment.
Drug Interactions with Braftovi
1. Effects of Other Drugs on Braftovi
Potent or intermediate-potency CYP3A4 inhibitors: Avoid co-administration. If unavoidable, reduce the braftovi dose.
Potent CYP3A4 inducers: Avoid co-administration.
2. Effects of Braftovi on Other Drugs
Sensitive CYP3A4 substrates: Avoid co-administration with CYP3A4 substrates (including hormonal contraceptives). If unavoidable, refer to the CYP3A4 substrate product label.
Transporters: Dose adjustments may be necessary when co-administering with OATP1B1, OATP1B3, or BCRP substrates.
3. Medications that prolong the QT interval
Avoid concurrent use with medications known to prolong the QT/QTc interval.
Note: For detailed information, please refer to the original drug's package insert. Follow your doctor's instructions for specific medication use.
Storage of Cannefenib (Braftovi)
Store Cannefenib (Braftovi) at 20–25°C (temperature fluctuations within 15–30°C are permissible). Store in its original, tightly closed container with a desiccant.
