Drug updated on 9/4/2024
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.
Latest News
Summary
- Mekinist (trametinib) is indicated for the treatment of BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma in both treatment-naïve patients and in combination with dabrafenib. It is also indicated in combination with dabrafenib for adjuvant treatment following resection in melanoma patients with lymph node involvement, for metastatic non-small cell lung cancer, anaplastic thyroid cancer, and for unresectable or metastatic solid tumors in both adults and pediatric patients 1 year of age and older. Additionally, it is indicated in combination with dabrafenib for the treatment of pediatric patients 1 year of age and older with low-grade glioma requiring systemic therapy.
- This summary is based on the review of 22 systematic review(s)/meta-analysis(es). [1-22]
- In low-grade gliomas (LGG), the combination of trametinib and dabrafenib demonstrated an overall response rate (ORR) of 50% (95% CI: 35-65%) with a 6-month progression-free survival (PFS) rate of 87% and a 12-month PFS rate of 67%.
- In high-grade gliomas (HGG), the combination showed an ORR of 40% (95% CI: 29-51%), with a 6-month PFS rate of 67% and a 12-month PFS rate of 44%.
- For Stage III/IV cutaneous melanoma, trametinib combined with dabrafenib in a neoadjuvant setting showed very low-certainty evidence of increased overall survival (HR 0.28, 95% CI: 0.03 to 2.25) and time to recurrence (HR 0.02, 95% CI: 0.00 to 0.22).
- In neurofibromatosis type 1 (NF1) related nerve tumors, trametinib showed a pooled objective response rate (ORR) of 45.3% (95% CI: 28.9-62.1%) and a disease control rate (DCR) of 99.8% (95% CI: 95.5-100%).
- In patients with low-grade gliomas (LGG), 100% experienced Grade 1-4 adverse events when treated with trametinib combined with dabrafenib. In high-grade gliomas (HGG) patients, the incidence was 63%.
- For cutaneous melanoma, the combination of trametinib and dabrafenib generally had a lower risk of severe adverse events compared to other therapies, particularly vemurafenib and cobimetinib.
- In patients with neurofibromatosis type 1 (NF1) related nerve tumors, the most common adverse event observed was paronychia, occurring in 60.7% of patients treated with trametinib.
- Trametinib, especially when combined with dabrafenib, demonstrates different levels of effectiveness and safety across subgroups, including gliomas (low-grade and high-grade), stage III/IV cutaneous melanoma with BRAF V600 mutations, neurofibromatosis type 1 (NF1) with nerve tumors, and a specific non-small-cell lung cancer case with a rare BRAF mutation. Effectiveness and safety outcomes vary depending on the cancer type, stage, and treatment setting.
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 |