Trametinib: A Breakthrough Drug for BRAF-Mutated Cancers
Trametinib: A Breakthrough Drug for BRAF-Mutated Cancers
Trametinib (Mekinist) is a drug that belongs to a class of medications called kinase inhibitors. Kinases are proteins that play a key role in regulating various cellular processes, such as growth, division, survival, and migration. Some cancers have mutations in genes that encode kinases, which make them overactive and cause the cells to grow uncontrollably. Trametinib works by blocking a specific kinase called MEK, which is involved in a pathway called MAPK. This pathway is often activated by mutations in another gene called BRAF, which is found in about half of all melanomas and some other cancers1.
Trametinib was first approved by the Food and Drug Administration (FDA) in 2013 as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test2. Since then, trametinib has been approved for several other indications, either alone or in combination with another drug called dabrafenib (Tafinlar), which is also a kinase inhibitor that targets the BRAF protein directly2. These indications include:
- The combination of trametinib and dabrafenib for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations2.
- The combination of trametinib and dabrafenib for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations and involvement of lymph node(s), following complete resection3. This means that the drugs are given after surgery to reduce the risk of the cancer coming back.
- The combination of trametinib and dabrafenib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation2.
- The combination of trametinib and 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 options2.
- The combination of trametinib and dabrafenib for the treatment of adult and pediatric patients 6 years 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 options4. 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).
- Trametinib alone 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 therapy5.
The approval of trametinib for these indications was based on clinical trials that showed significant improvement in survival, response rate, and disease control compared to placebo or standard chemotherapy. The most common side effects of trametinib include rash, diarrhea, lymphedema, fatigue, nausea, fever, joint pain, headache, vomiting, constipation, cough, and muscle pain. Some serious side effects include bleeding, colitis, heart problems, eye problems, lung problems, skin problems, liver problems, high blood sugar levels, and new skin cancers2.
Trametinib is taken as a tablet or oral solution once daily at least 1 hour before or at least 2 hours after a meal. The dose may vary depending on the indication, the combination partner, and the patient’s weight. Patients should have their blood pressure, heart function, liver function, blood sugar levels, and eye exams monitored regularly while taking trametinib. Patients should also avoid sun exposure and use sunscreen while taking trametinib2.
Trametinib is a breakthrough drug that has changed the landscape of treatment for patients with BRAF-mutated cancers. By targeting a specific molecular pathway that drives tumor growth, trametinib can offer more effective and less toxic options than conventional chemotherapy. Trametinib is also being studied in combination with other drugs for other types of cancers that have BRAF mutations or other alterations in the MAPK pathway.
If you have cancer that has spread beyond the skin, you should ask your doctor if your tumor has a BRAF mutation. If it does, you may benefit from trametinib alone or in combination with dabrafenib. Your doctor will discuss with you the best treatment options for your specific case.