Title |
Trametinib: a MEK inhibitor for management of metastatic melanoma
|
---|---|
Published in |
OncoTargets and therapy, August 2015
|
DOI | 10.2147/ott.s72951 |
Pubmed ID | |
Authors |
Iwona Lugowska, Hanna Koseła-Paterczyk, Katarzyna Kozak, Piotr Rutkowski |
Abstract |
This review presents the current data on the efficacy and safety of the selective mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib in patients with metastatic BRAF V600-positive melanoma. The pharmacological, safety, and efficacy data come from the Phase I, II, and III studies of trametinib monotherapy, as well as those in combination with the BRAF inhibitor dabrafenib. The most common adverse effects of trametinib therapy are rash, dermatitis, diarrhea, and fatigue. The Phase III METRIC study showed significant improvement in overall survival and progression-free survival in favor of trametinib over standard dacarbazine or paclitaxel chemotherapy. Therefore, trametinib was approved by the US Food and Drug Administration and European Medicines Agency as a single agent for the treatment of patients with V600E-mutated metastatic melanoma. Progression-free survival and response rates for trametinib monotherapy were lower than those noted with BRAF inhibitors. The second step in developing trametinib was to use the combination of trametinib with the BRAF inhibitor, eg, dabrafenib, to postpone the progression on MEK or BRAF inhibitors. The recently published data showed significant improvement in overall survival and progression-free survival in favor of the combination of trametinib and dabrafenib over vemurafenib therapy or dabrafenib alone, with good tolerance. The US Food and Drug Administration has approved the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma, and their use seems to be currently the best approach. While BRAF-MEK inhibition is a standard, molecular targeted therapy in BRAF-mutated melanomas, its future utility has to be established in the rapidly changing landscape of immunotherapeutics. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Netherlands | 1 | <1% |
United States | 1 | <1% |
Poland | 1 | <1% |
Unknown | 187 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 34 | 18% |
Student > Ph. D. Student | 32 | 17% |
Student > Master | 25 | 13% |
Researcher | 16 | 8% |
Student > Doctoral Student | 11 | 6% |
Other | 23 | 12% |
Unknown | 50 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 57 | 30% |
Medicine and Dentistry | 27 | 14% |
Agricultural and Biological Sciences | 19 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 18 | 9% |
Chemistry | 5 | 3% |
Other | 15 | 8% |
Unknown | 50 | 26% |