Drug updated on 12/11/2024
| Dosage Form | Tablet (oral; 0.5 mg, 2 mg) |
| Drug Class | Kinase inhibitors |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for the treatment of BRAF-inhibitor treatment-nave patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA approved test
- Indicated in combination with dabrafenib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test
- Indicated in combination with dabrafenib, for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection
- Indicated in combination with dabrafenib, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test
- Indicated in combination with dabrafenib, for the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options
- Indicated in combination with dabrafenib, for the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options
- This indication is approved under accelerated approval based on overall response rate and duration of response
- Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)
- Indicated in combination with dabrafenib, for the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.
Latest News
Summary
- This summary is based on the review of 21 systematic review(s)/meta-analysis(es). [1-21]
- BRAF-Mutant Melanoma: Dabrafenib + trametinib demonstrates high efficacy and manageable safety profiles, significantly prolonging overall survival (OS) and progression-free survival (PFS) compared to monotherapies and other combination therapies.
- Acral Melanoma: Adjuvant therapy with dabrafenib + trametinib achieves high rates of 12-month recurrence-free survival (RFS) in BRAF-mutated cases, indicating effectiveness in this specific population.
- Anaplastic Thyroid Cancer: Evidence supports the combination of dabrafenib + trametinib, showing a median OS of 6.37 months and a median PFS of 5.50 months in real-world clinical practice, highlighting its utility beyond melanoma.
- Adverse Events (AEs): The combination of dabrafenib + trametinib was associated with a high incidence of AEs, reporting 50% AEs and 43% death events in BRAF V600-mutant glioma patients. Common AEs included rash, cutaneous squamous-cell carcinoma (cSCC), alopecia, keratoacanthoma (KA), hyperkeratosis (HK), and pruritus.
- Comparison to Other Drugs: Encorafenib + binimetinib showed fewer serious adverse events and lower rates of discontinuations due to AEs compared to dabrafenib + trametinib. In contrast, nivolumab + ipilimumab had the highest risk of AEs among the therapies compared.
- BRAF-Mutant Melanoma: Dabrafenib + trametinib is recommended for both adjuvant and unresectable/metastatic settings in patients with BRAF-mutant cutaneous melanoma, demonstrating high efficacy and manageable safety profiles across multiple studies.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Mekinist (trametinib) Prescribing Information. | 2024 | Novartis Pharmaceuticals Corporation, East Hanover, NJ |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Practical Recommendations for the Manipulation of Kinase Inhibitor Formulations to Age-Appropriate Dosage Forms. | 2022 | Pharmaceutics |
| European consensus-based interdisciplinary guideline for melanoma. part 2: treatment - update 2022. | 2022 | European Journal of Cancer |
| Systemic therapy for melanoma: ASCO guideline. | 2020 | Journal of Clinical Oncology |
| Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. | 2019 | Annals of Oncology |