Dabrafenib (Tafinlar®) + Trametinib (Mekinist®) Adjuvant Therapy
Even after successfully removing melanoma through surgery, patients may be at risk for melanoma coming back. Dabrafenib (Tafinlar®) + Trametinib (Mekinist®) in the adjuvant setting reduces this risk by blocking the activity of certain molecules within cancer cells that control cell growth.
In April 2018, the U.S. Food and Drug Administration (FDA) approved the use of the combination of dabrafenib + trametinib for the treatment of melanoma patients with BRAF V600E or V600K mutations and lymph node involvement following complete resection.Treatment after surgery is known as adjuvant therapy. The goal of adjuvant therapy is to reduce the risk of melanoma coming back after surgery.
Patients with Stage III melanoma usually undergo surgery to remove the primary melanoma and the nearby lymph nodes. With adjuvant therapy after surgery, patients can reduce their risk of melanoma returning or improving what doctor’s call recurrence-free survival (RFS).
The FDA approval for the use of dabrafenib + trametinib in the adjuvant setting is based on results from the COMBI-AD study published in the New England Journal of Medicine. In the study, dabrafenib + trametinib was compared to placebo in patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations. The combination vs. placebo improved recurrence-free survival at three years (58% vs 39%) and the three-year overall survival rate (86% vs 77%) was highly encouraging. Twenty-six percent of patients who received dabrafenib + trametinib discontinued treatment due to side effects.
Learn more about adjuvant therapy for high-risk melanoma (stages IIB, IIC, III and IV).
What Is Dabrafenib (Tafinlar®) + 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
Targeted therapy works by shutting down molecules inside tumor cells to slow their growth. Dabrafenib blocks the activity of a mutated version of a molecule called BRAF and trametinib blocks the activity of the MEK molecule that works in coordination with BRAF. Each drug was approved separately by the FDA to treat advanced BRAF-mutant metastatic melanoma in 2013 and the two were approved in combination in 2014.
In addition to its use for the adjuvant therapy of melanoma, the combination of dabrafenib + trametinibis used to treat advanced melanoma that is unresectable or has spread to organs and other parts of the body. To learn more about the use of dabrafenib + trametinib for advanced melanoma, click here.
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.
How Is Dabrafenib (Tafinlar®) + Trametinib (Mekinist®) Given?
Patients take both medications orally (swallowing by mouth).
- The recommended dose for dabrafenib is 150 mg twice each day.
- The recommended dose for trametinib is 2 mg once each day, via 0.5 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 Adjuvant Dabrafenib (Tafinlar®) + Trametinib (Mekinist®)?
In the adjuvant setting, the goal of Dabrafenib + Trametinib is to reduce the risk of melanoma returning following surgery.
What Should I Ask My Doctor About Adjuvant Dabrafenib (Tafinlar®) + Trametinib (Mekinist®)?
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?
Need Help Paying for Dabrafenib (Tafinlar) + Trametinib (Mekinist)?
Patient Assistant Programs (PAPs) are designed so that you still have access to the treatments you need, in any financial circumstance. Learn more about the manufacturer’s patient assistance program and other options here.
Latest Treatments for Melanoma
Learn more about the latest, most effective treatments for patients who have melanoma:
- Other types of immunotherapy, including:
- Targeted therapy
- Combination therapy
- Adjuvant therapy for high-risk melanoma
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: January 2018
Last reviewed: May 2016
Reviewers: John Kirkwood, Lynn Schuchter, Louise Perkins