Dabrafenib (Tafinlar®) + Trametinib (Mekinist®)
Targeted therapy for advanced melanoma blocks the activity of certain molecules within cancer cells that control cell growth. Two such drugs, dabrafenib (Tafinlar) and trametinib (Mekinist), shrink tumors and help patients with advanced melanoma live longer.
Through clinical trials, cancer researchers have found that combining dabrafenib and trametinib can treat advanced melanoma more effectively than either medication on its own. The combination also produces less serious side effects than the single drugs used alone.
What Are Dabrafenib (Tafinlar) and Trametinib (Mekinist)?
Dabrafenib is a BRAF (pronounced bee-raff) inhibitor, and trametinib is a MEK (pronounced meck) inhibitor. Both medications:
- Are a type of targeted therapy known as signal transduction inhibitors
- Help slow or stop the growth and spread of melanoma cells
How Do Dabrafenib and Trametinib Work Together?
Dabrafenib blocks the activity of a mutated version of a molecule called BRAF. Trametinib blocks the activity of an enzyme molecule called MEK. Both BRAF and MEK are key molecules that help regulate cell growth.
Certain mutations in BRAF signal cells to develop abnormally and divide out of control. These cells can grow into a melanoma tumor. About half of all melanomas have a BRAF mutation.
MEK receives signals from BRAF and other molecules in the cell. Scientists have found that blocking MEK alone is not as effective as blocking BRAF and MEK at the same time.
The combination of dabrafenib and trametinib blocks the signaling pathway of the abnormal BRAF molecules. This action slows or stops the out-of-control cell growth:
- Dabrafenib targets the V600E-mutated BRAF molecule to block its signaling.
- Trametinib targets MEK to block signaling from the V600E- or V600K-mutated BRAF molecule via the MEK molecule.
Which Patients May Benefit from Dabrafenib and Trametinib?
In 2014, the FDA approved the use of dabrafenib in combination with trametinib to treat patients who have advanced stages of melanoma:
- Stage III that is unresectable (unable to be completely removed by surgery)
- Stage IV, also known as metastatic (melanoma cells that have spread to organs and other parts of the body)
Dabrafenib with trametinib as combination therapy works only in patients whose melanoma has tested positive for the BRAF V600E or V600K mutation. If you have advanced melanoma, your physician will test you for specific genetic mutations before prescribing this medication combination. The physician will send a biopsy (sample of cancer tissue removed from your body) to a special lab for analysis.
How Are Dabrafenib and Trametinib Given?
Patients take both medications orally (swallowing by mouth).
- The recommended dose for dabrafenib is 150 mg twice each day, via 50 or 75 mg capsules.
- The recommended dose for trametinib is 2 mg once each day, via 0.5, 1, or 2 mg tablets.
- Depending on how you respond to treatment, your physician may adjust your doses.
- Patients usually continue to take these medications for a period of time, until their melanoma worsens or they experience unacceptable side effects.
What Are the Goals of Dabrafenib and Trametinib?
The combination of dabrafenib and trametinib targets specific molecules that regulate cancer cell growth, with the goals of :
- Slowing the growth or spread of melanoma
- Shrinking melanoma tumors
- Helping patients live longer
Results from two Phase III clinical trials in 2014 showed improved patient outcomes for patients taking dabrafenib and trametinib compared with:
- Patients taking vemurafenib (Zelboraf)
- Patients taking dabrafenib and a placebo
Melanoma treatments, like dabrafenib and trametinib, have side effects, which can sometimes be serious. Patients should talk with their physician to learn more about the side effects of these and other melanoma treatment options.
What Should I Ask My Doctor About Dabrafenib and Trametinib?
Not all treatments work for all patients with melanoma because everyone is different. If you are interested in learning more about the combination of dabrafenib and trametinib, here are some questions you should ask your physicians:
- Will my melanoma tumor be tested for BRAF genetic mutations?
- Am I eligible for dabrafenib and trametinib?
- What is your experience with dabrafenib and trametinib?
- Is this combination therapy a good option for my melanoma treatment?
- Is there an alternative to dabrafenib and trametinib for me?
- How successful has the combination been for patients like me?
- What are the side effects of dabrafenib and trametinib?
- Are there any clinical trials for the combination therapy that I should consider?
- What other treatments are FDA-approved for treating advanced melanoma?
- What are the risks and benefits of the available treatment options?
- What are the goals for treatment?
- How long will I stay on this treatment?
Latest Treatments for Advanced Melanoma
Learn more about the latest, most effective treatments for patients who have advanced melanoma:
- Other types of combination therapy, including:
- Targeted therapy
- Adjuvant therapy
Since its founding in 2007, the Melanoma Research Alliance has awarded over $100 million to research aimed at better preventing, diagnosing, and treating melanoma. Learn more about our funded research.
Last Updated: May 2016
Reviewed by: Paul Chapman, Antoni Ribas, Louise Perkins