Treatment Name: Dabrafenib (Tafinlar®) + Trametinib (Mekinist®)
Dabrafenib (Tafinlar®) + Trametinib (Mekinist®) is a Chemotherapy Regimen for Melanoma
How does Dabrafenib (Tafinlar®) and Trametinib (Mekinist®) work?
Each of the medications in dabrafenib and trametinib are designed to not only kill melanoma cells, but prevent the development of new skin cancers. They work by shutting off signals within the cancer cell that constantly tell the cells to grow and divide. These signals are known as “RAF” and “MEK” signals.
Goals of therapy:
Dabrafenib and trametinib are chemotherapy drugs taken to shrink melanoma cells and decrease symptoms from melanoma. The combination of dabrafenib + trametinib is not commonly given with the goal of cure.
Usual dabrafenib and trametinib starting doses:
- Dabrafenib 150 mg (three 50 mg capsules or two 75 mg capsules) by mouth TWICE Daily
- Dabrafenib is taken at least one hour before a meal or at least 2 hours after a meal
- Each dose of dabrafenib should be taken about 12 hours apart
- Trametinib 2 mg oral tablet by mouth Once Daily
- Trametinib is taken at least one hour before a meal or at least 2 hours after a meal
*It is important to note, one of these medications (dabrafenib) is taken TWICE daily, while the other (trametinib) is taken ONCE daily. The once daily trametinib dose may be taken at the same time as one of the dabrafenib doses. Dabrafenib and trametinib are usually taken at home. Treatment is continued every day until it no longer works or until unacceptable side effects occur.
In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported dabrafenib + trametinib side effects are shown here. Side effects sometimes have percentage ranges [example: 20 – 35%] because they differed between clinical studies:
- Fever (52 - 53%)
- Nausea (20 - 35%)
- Diarrhea (18 - 32%)
- Chills (28 - 31%)
- Vomiting (14 - 29%)
- Fatigue (27%)
- Rash (22 - 24%)
- Joint pain (16 - 24%)
- Headache (19%)
- Fluid retention or swelling of legs (14%)
- Dry skin (9%)
- Decreased heart function (8%)
- Itching (7%)
- Acne-like skin rash (6%)
- Hair loss* (5 - 6%)
- Thickening of the outer layer of skin (4 - 6%)
- Redness, swelling, and blisters on palms of hands and soles of feet (4 - 6%)
- Sensitivity to sunlight (4%)
- Benign skin tumor (1 - 2%)
- New squamous cell carcinoma skin cancer (1%)
- Change in vision (1 - 2%)
*Hair loss from dabrafenib and trametinib is almost always mild, not obvious from a distance, and seen only on close inspection. A different hair style can help cover some hair loss, and a wig or hair piece is usually not required.
Bleeding can occur when dabrafenib is taken with trametinib. Tell your doctor immediately if you have any signs or symptoms of bleeding.
On average, 11 - 13% of patients discontinue dabrafenib and trametinib treatment due to unacceptable side effects.
How often is monitoring needed?
Labs (blood tests) may be checked before treatment and periodically during treatment until stable. Labs often include: a blood test called “BRAF V600E mutation” or “BRAF V600K mutation”, which helps predict the chance of responding to these medications, Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), plus any others your doctor may order.
You and your doctor will also monitor your skin for new skin lesions (abnormal growths). Tell your doctor right away if any new skin lesions are seen.
How often is imaging needed?
Imaging may be checked before treatment then approximately every 8 weeks for the first year, then every 12 weeks thereafter, or until stable. Imaging may include: X-rays, magnetic resonance imaging (MRI), computerized tomography (CT) scans, or positron emission tomography (PET) scans. Echocardiograms (Echo) to check heart function are typically performed prior to starting treatment, one month after starting treatment, then every 2 to 3 months thereafter. An eye exam may also be recommended before starting treatment with dabrafenib + trametinib. Notify your doctor if you experience any change in vision, eye pain, or increased sensitivity to light.
How might blood test results/imaging affect treatment?
Imaging can be used to see if the melanoma is getting smaller or spreading. If breathing or chest pain is noticed, imaging can also help detect a blood clot in the lungs (pulmonary embolism, or PE). Depending upon the results, your doctor may advise to continue dabrafenib + trametinib as planned, reduce the dose of future treatments, delay treatment until a side effect goes away, or switch to an alternative therapy.
- A specific test, approved by FDA, known as the “BRAF V600E mutation,” or “V600K” is recommended before starting dabrafenib therapy to determine whether dabrafenib will likely kill melanoma cells. If the mutation is NOT detected, then the chance of dabrafenib working may be low
- When fever occurs, it usually lasts for about three days, although it can last for much longer. If fever is experienced, the first fever usually occurs about one month after starting dabrafenib and trametinib, but may occur sooner or later than this time period. Dabrafenib therapy should be temporarily withheld if the temperature reaches 101.3°F or higher. A low dose of prednisone may be prescribed for 5 or more days if the temperature does not return to normal after three days
- As many as 11% of patients who take dabrafenib alone may develop a second type of skin cancer known as “squamous cell carcinoma.” When combined with trametinib, the number of patients that develop new skin cancers is approximately 3% and these usually develop between 7 – 8 months after starting treatment. Additional surgical procedures may be needed to remove these cancers and therapy with dabrafenib may usually continue. Skin exams are usually done before starting therapy, every two months during therapy, and for up to 6 months after stopping treatment
- Sun sensitivity may occur with dabrafenib. When outside, patients should wear protective clothing, suncscreen with SPF 30 or greater, and use a lip balm with SPF 30 or greater
- An eye problem known as “uveitis” can develop in about 2% of patients taking dabrafenib with trametinib. Uveitis may cause problems tolerating any light as well as blurred vision. Treatment may consist of steroid eye drops, with or without a medication to dilate the pupils. Other very rare but serious eye problems such as retinal detachment and blockage of the veins in the eye have also been reported
- Dabrafenib may lose effectiveness if taken with medicines for heartburn such as antacids (example: Tums®), proton pump inhibitors (example: omeprazole (Prilosec®)) or H2-antagonists (famotidine, ranitidine). Talk with your doctor or pharmacist about how best to take these two medicines together
- Painful redness, blistering, and peeling skin reaction on the palms of your hands and on the soles of your feet may develop. This is known as Hand-Foot Syndrome. Ways to help reduce the risk of experiencing Hand-Foot Syndrome include using a non-alcoholic moisturizer daily on your hands and feet, avoid wearing gloves, avoid prolonged exposure to hot water, and avoid activities that put pressure or friction on your hands and feet such as golf or tennis while being treated with dabrafenib + trametinib
- Dabrafenib may decrease the effectiveness of oral birth control pills. Women of child bearing age should talk to their doctor about alternative forms of contraception
- A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
- Clinical trials may exist for melanoma. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications
Patient Assistance & Co-payment Coverage
Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for Dabrafenib (Tafinlar®) + Trametinib (Mekinist®), we have provided links that may help.
Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for Dabrafenib (Tafinlar®) + Trametinib (Mekinist®). Depending upon your income, they may be able to help cover the cost of:
For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.
- If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.
Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as Dabrafenib (Tafinlar®) + Trametinib (Mekinist®) and are the best source to help you understand drug cost.
- Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.
What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.
Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.
Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.
Learn more about pursuing emotional wellness while receiving treatment with Dabrafenib (Tafinlar®) + Trametinib (Mekinist®)
What is Melanoma?
A disease of the melanocytes found in the skin. Melanoma is a rare diagnosed condition. The risk of melanoma may increase with increased exposure to UV light. Melanoma may be hereditary. Melanoma may occur in areas that do not receive much sun light, such as the bottom of a foot. It may also occur in places other than skin, such as the eye. The stage of melanoma can vary at diagnosis and throughout treatment. Stages of melanoma include Stage I, II, III, and IV. The effectiveness of the treatment may depend upon the stage at diagnosis.
NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose which therapy is appropriate for you.
What does "Cure" mean?
The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, doctors use the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.
Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.
If you are interested in reading the clinical trials results, please click on reference below:
1) Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386:444-451.
2) Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30-39.
What is a CBC?
A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.
2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.
3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.
What is a CMP?
A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status, 2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.
Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein
13) Serum glucose
14) Serum calcium