Trametinib

Medical uses

Trametinib, as monotherapy or in combination with dabrafenib is indicated for the treatment of melanoma and glioma.

History

Clinical trial data demonstrated that resistance to single-agent trametinib often occurs within 6 to 7 months. To overcome this, trametinib was combined with the BRAF inhibitor dabrafenib. As a result of this research, on 8 January 2014, the FDA approved the combination of dabrafenib and trametinib for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma. On 1 May 2018, the FDA approved the combination dabrafenib/trametinib as an adjuvant treatment for BRAF V600E-mutated, stage III melanoma after surgical resection based on the results of the COMBI-AD phase 3 study, making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.

Society and culture

Legal status

In November 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Spexotras, intended for the treatment of low- and high-grade glioma (LGG and HGG). The applicant for this medicinal product is Novartis Europharm Limited. Spexotras was approved for medical use in the European Union in January 2024.

Research

Trametinib had good results for metastatic melanoma carrying the BRAF V600E mutation in a phase III clinical trial. In this mutation, the amino acid valine (V) at position 600 within the BRAF protein has become replaced by glutamic acid (E) making the mutant BRAF protein constitutively active.

Trametinib has been used off label to treat various RASopathies, including Noonan Syndrome and Primary Intestinal Lymphangiectasia.

References

References

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11. (November 2012). "Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations". The New England Journal of Medicine.
12. (9 January 2014). "Dabrafenib/Trametinib Combination Approved for Advanced Melanoma". OncLive.
13. (November 2017). "Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma". The New England Journal of Medicine.
14. "FDA Approves Adjuvant Combo for BRAF+ Melanoma". WebMD LLC.
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17. (November 2022). "Successful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan Syndrome". European Journal of Medical Genetics.
18. (March 2021). "MEK inhibitors in RASopathies". Current Opinion in Oncology.