Drug updated on 4/24/2024
| 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-naïve 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.
Summary
- Trametinib (Mekinist) is indicated for the treatment of various conditions including unresectable or metastatic melanoma with BRAF V600E or V600K mutations, non-small cell lung cancer (NSCLC), anaplastic thyroid cancer (ATC), and low-grade glioma in both adult and pediatric patients. It can be used alone or in combination with dabrafenib.
- A total of 22 studies were reviewed to gather information about trametinib's safety and efficacy across different indications.
- In terms of treating gliomas, particularly low-grade tumors, trametinib shows promising anti-tumor efficacy, but toxicity significantly limits tolerability, indicating a need for further research on safe administration protocols.
- The evidence regarding neoadjuvant treatment for stage III or IV melanoma using trametinib combined with dabrafenib is uncertain. This regimen may slightly increase adverse events compared to no neoadjuvant treatment.
- For health-related quality of life among melanoma patients, inconsistencies are noted between immune checkpoint inhibitors and targeted therapies like trametinib plus dabrafenib; some studies found no significant change from baseline, indicating more specific patient-reported outcome measures are needed.
- Network meta-analyses suggest that nivolumab plus ipilimumab show the most significant improvement in recurrence-free survival when used as adjuvant therapy after resectioning melanomas. However, combining trametinib with dabrafenib also provides a promising strategy, though it needs more supporting evidence.
- When comparing adverse events across treatments for BRAF V600-mutant melanoma: immunotherapy generally has better acceptability than most targeted therapies such as single-agent dabrafenib combined with trametinib due to a lower risk of adverse events, affirming its place in the treatment landscape considering safety profiles.
- For patients with BRAF V600E mutated Anaplastic Thyroid Carcinoma (ATC), dabrafenib in combination with trametinib has demonstrated efficacy, underscoring the importance of selecting targeted therapies based on molecular profiling of tumors to improve patient outcomes.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Mekinist (trametinib) Prescribing Information. | 2023 | Novartis Pharmaceuticals Corporation, East Hanover, NJ |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| European consensus-based interdisciplinary guideline for melanoma. part 2: treatment - update 2022. | 2022 | European Journal of Cancer |
| Practical Recommendations for the Manipulation of Kinase Inhibitor Formulations to Age-Appropriate Dosage Forms. | 2022 | Pharmaceutics |
| 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 |