Encorafenib exerts its anti-tumor effect by specifically inhibiting the activity of BRAF mutant protein, thereby blocking tumor cell proliferation and survival signaling pathways.
Recommended Adult Dosage for Encorafenib
1. Non-Small Cell Lung Cancer
Encorafenib, in combination with binimetinib, is administered orally once daily at a dose of 450 mg until disease progression or unacceptable toxicity occurs.
2. Metastatic Melanoma
Encorafenib, in combination with binimetinib, is administered orally once daily at a dose of 450 mg until disease progression or unacceptable toxicity occurs.
3. Colorectal Cancer
Encorafenib, in combination with cetuximab, is administered orally once daily at a dose of 300 mg until disease progression or unacceptable toxicity occurs.
Precautions for Encorafenib
1. Pre-treatment Precautions
(1) Patient Screening
Before initiating treatment, confirm the presence of the indicated BRAF mutation in a tumor (or plasma, if applicable) specimen using a test approved by the U.S. Food and Drug Administration (FDA).
(2) Limitations of Use
This drug is not indicated for the treatment of wild-type BRAF melanoma, wild-type BRAF colorectal cancer, or wild-type BRAF non-small cell lung cancer.
2. Precautions During Treatment
(1) Route of Administration
Oral administration, with or without food.
(2) Management of Missed Doses
If a dose is missed, do not take an extra dose if less than 12 hours have passed since the next dose.
(3) Management of Vomiting
If vomiting occurs after administration, do not take an extra dose; continue with the next dose as scheduled.
Encorafenib Monitoring Recommendations
Cardiovascular
Monitor left ventricular dysfunction (before treatment, 1 month after treatment, and every 2-3 months thereafter); monitor for QT interval prolongation or its risk (as needed, before and during treatment).
Skin
Skin assessment (before treatment, every 2 months during treatment, and 6 months after discontinuation).
Liver
Liver function tests (as needed, before and during treatment).
Metabolism
Electrolytes (before and during treatment; correct abnormalities as needed).
Ophthalmology
Ophthalmological assessment (regularly during treatment).
Oncology
Monitor for new non-cutaneous malignancies (before, during, and after treatment).
Dose Adjustment for Adverse Reactions of Encorafenib
1. Melanoma or Non-Small Cell Lung Cancer
Stepwise Dose Reduction:
First Dose Reduction: Reduce to 300 mg orally daily.
Second Dose Reduction: Reduce to 225 mg orally daily.
Third Dose Reduction: If 225 mg orally daily cannot be tolerated, permanently discontinue treatment.
If Bimetinib Treatment is Discontinued: Reduce the encorafenib dose to a maximum of 300 mg orally daily until combination therapy is resumed.
2. Colorectal Cancer
Stepwise Dose Reduction:
First Dose Reduction: Reduce to 225 mg orally daily.
Second Dose Reduction: Reduce to 150 mg orally daily.
Third Dose Reduction: If 150 mg orally daily cannot be tolerated, permanently discontinue treatment.
If Cetuximab Treatment is Discontinued: Discontinue encorafenib treatment.
Dose Adjustment of Encorafenib in Specific Populations
1. Dose Adjustment for Patients with Renal Impairment
Mild or moderate renal impairment (creatinine clearance 30-89 mL/min): No dose adjustment required.
Severe renal impairment (creatinine clearance <30 mL/min): Recommended dose not yet determined.
2. Dose Adjustment for Patients with Hepatic Impairment
(1) Baseline Hepatic Abnormalities
Mild hepatic impairment (Child-Pugh A): No dose adjustment required.
Moderate or severe hepatic impairment (Child-Pugh B or C): Recommended dose not yet determined.
(2) Management of Hepatotoxicity (Elevated AST/ALT) During Treatment
Grade 2 AST/ALT elevation: Maintain the current dose; if there is no improvement within 4 weeks, discontinue treatment until it returns to Grade 0-1 or pre-treatment/baseline levels, then restart treatment at the original dose.
Relapsed grade 2 AST/ALT or first occurrence of grade 3 AST/ALT elevation: Discontinue medication for up to 4 weeks; if recovery to grade 0-1 or pre-treatment/baseline levels, restart treatment at a reduced dose; if no improvement, permanently discontinue medication.
First occurrence of grade 4 AST/ALT elevation: Permanent discontinuation or treatment suspension for up to 4 weeks may be considered. If recovery to grade 0-1 or pre-treatment/baseline levels, restart treatment at a reduced dose; if no improvement, permanently discontinue medication.
Relapsed grade 3 AST/ALT elevation: Consider permanent discontinuation.
Relapsed grade 4 AST/ALT elevation: Permanent discontinuation.
Encorafenib Specific Adverse Reaction Dosage Adjustment
1. Newly diagnosed malignant tumors
Non-cutaneous RAS mutation-positive malignant tumors: Permanently discontinue this drug.
Curricular malignant tumors: Dosage adjustment is not recommended.
2. Cardiomyopathy
(1) For symptomatic congestive heart failure or a left ventricular ejection fraction (LVEF) that is more than 20% lower than baseline and below the lower limit of normal (LLN), reduce the dose by one level.
(2) If there is improvement in at least LLN with an absolute decrease of 10% or less from baseline, continue treatment at the reduced dose.
(3) If there is no improvement, discontinue treatment until improvement is achieved in at least LLN with an absolute decrease of 10% or less from baseline; then resume treatment at the reduced dose or reduce the dose by another level.
3. Uveitis (including iritis and iridocyclitis)
Grades 1-3: If grade 1 or 2 uveitis is unresponsive to specific ocular treatment, or if it is grade 3 uveitis, discontinue this medication for up to 6 weeks. If there is improvement, resume treatment at the same dose or the reduced dose; if there is no improvement, permanently discontinue this medication.
Grade 4: Permanently discontinue treatment.
4. QTc Interval Prolongation
QTcF exceeding 500 milliseconds (ms), an increase of 60 ms or less from baseline: Discontinue this medication until QTcF reaches 500 ms or less; then resume treatment at a reduced dose. If more than one relapse occurs, permanently discontinue this medication.
QTcF exceeding 500 ms, an increase of more than 60 ms from baseline: Permanently discontinue this medication.
5. Skin Reactions
Grade 2: If there is no improvement within 2 weeks, discontinue this medication until Grade 0 or 1; resume treatment at the same dose.
Grade 3: Discontinue this medication until Grade 0 or 1; if this is the first occurrence, resume treatment at the same dose; if this is a relapse, resume treatment at a reduced dose.
Grade 4: Permanently discontinue this medication.
6. Other Adverse Reactions (including bleeding and hand-foot skin reactions)
First occurrence of Grade 2 relapse or any Grade 3: Discontinue this medication for up to 4 weeks; if improvement to Grade 0 or 1, or return to pre-treatment/baseline levels, resume treatment at a reduced dose. If no improvement, permanently discontinue this medication.
First occurrence of any Grade 4: Permanently discontinue this medication or suspend treatment for up to 4 weeks. If improvement to Grade 0 or 1, or return to baseline levels, resume treatment at a reduced dose; if no improvement, permanently discontinue this medication.
Grade 3 relapse: Consider permanent discontinuation of this medication.
Grade 4 relapse: Permanently discontinue this medication.
Encorafenib in Concomitant Use with CYP4503A4 Inhibitors
Dose Reduction During Concomitant Use with Intermediate or High-Potency CYP4503A4 Inhibitors:
1. Current dose is 450 mg daily.
Intermediate-potency inhibitor: Reduce to 225 mg daily.
Strong inhibitor: Reduce to 150 mg daily.
2. Current dose: 300 mg daily.
Intermediate inhibitor: Reduce to 150 mg daily.
Strong inhibitor: Reduce to 75 mg daily.
3. Current dose: 225 mg daily.
Intermediate or strong inhibitor: Reduce to 75 mg daily.
4. Current dose: 150 mg daily.
Intermediate or strong inhibitor: Reduce to 75 mg daily.
