Clinical trials advance science for patients with melanoma

(BPT) - Your skin is the largest organ of your body. And, like other parts of the body, it can get cancer. Melanoma is a rare form of skin cancer, and if caught early is often treatable. When it spreads to other parts of the body, the cancer is advanced – stage III or IV. Advanced stages of melanoma are harder to treat.

Cancers like melanoma can be caused by mutations, or changes, in the DNA of skin cells. In melanoma, these mutations can happen randomly or through ongoing exposure to the sun and UV rays. When this type of damage happens, it can lead to uncontrolled cell growth and may cause cancer cells to spread. One of the most common changes in melanoma cells that increase tumor cell growth is a BRAF mutation. Approximately one in two people diagnosed with melanoma have a BRAF mutation in their tumor cells.

Researchers are working to better understand the role of mutations like BRAF in melanoma. When people with melanoma participate in research and clinical trials, it helps to advance the science. Scientific advancements have led to more treatment options for people living with stage III and IV melanoma.

Read the Q&A below to learn more about this type of melanoma and important information to consider when you discuss with your doctor, including safety and potential long-term benefits shown in a clinical trial of a targeted therapy to treat stage III melanoma after surgery.

Q: How many people get melanoma and what role do gene alterations play in melanoma?

A: Approximately 100,000 adults in the United States will be diagnosed with melanoma in 2020 and approximately 6,850 people will die from the disease. Melanoma is a complex disease; changes or alterations to the genes play a role in its progression. Approximately one in two people diagnosed with melanoma have a BRAF mutation in their tumors, which is a specific change in the BRAF gene that may lead to the growth and spread of cancer cells. Biomarker testing can determine whether a tumor has a BRAF mutation.

Q: Why is biomarker testing and knowing your BRAF status so important for melanoma?

A: One of the most important things people diagnosed with melanoma can do is speak to their doctor about getting a biomarker test. The biomarker test helps people learn their BRAF mutation status. When the doctor and the patient know the BRAF mutation status, it helps identify all possible treatment options and may help make an informed treatment plan. People with a BRAF mutation may be candidates for therapies that target the mutation.

For example, one Phase III study that included patients with BRAF+, stage III melanoma showed the benefits of taking Tafinlar^® (dabrafenib) plus Mekinist^® (trametinib) for one year after having surgery to remove melanoma. At first analysis of this data, the results showed that the combination of Tafinlar plus Mekinist reduced the risk of relapse or death by 53% compared to placebo.

Later on, during an updated analysis, at five years, an estimated 52% of patients treated with Tafinlar plus Mekinist were alive without their cancer coming back compared to 36% of those who were treated with two placebo (pills with no active medication). During this update, it showed that there was a 49% reduction in risk of relapse or death.

Q: What do clinical experts say about a treatment for BRAF-mutated melanoma following surgery?

A: Researchers recently announced results from the COMBI-AD study published in the New England Journal of Medicine in September 2020. The 5-year results showed treatment with Tafinlar^® (dabrafenib) plus Mekinist^® (trametinib) for one year after surgery for BRAF+ stage III melanoma may result in relapse-free survival for some patients. An estimated 52% of patients treated with Tafinlar plus Mekinist were alive without their cancer coming back compared to 36% of those who were treated with two placebo (pills with no active medication). Information about side effects, some of which can be severe, for Tafinlar plus Mekinist are included at the end of this article.

Q: What does the COMBI-AD study mean for patients with stage III melanoma?

A: Some patients who have their melanoma removed by surgery still face the potential risk of their cancer coming back. Patients who have BRAF-positive stage III melanoma may be at a higher risk of their cancer coming back.

The findings from COMBI-AD support the important role a targeted therapy like Tafinlar plus Mekinist may play after surgery.

Q: What should people know about the safety results of the COMBI-AD study?

A: The COMBI-AD study helped researchers and physicians understand the side effects seen with treatment with Tafinlar plus Mekinist. Tafinlar plus Mekinist, in combination, may cause serious side effects. As part of informed treatment decision-making, patients and their physicians should review and discuss medication risks and benefits.

Some of the side effects can be severe and lead to death. Some of the side effects can cause patients to pause or completely stop taking their treatment. Patients should immediately talk to their doctor or healthcare provider if they experience any side effect. Please review the Important Safety Information towards the end of this article and visit us.tafinlarmekinist.com for the full Prescribing Information for Tafinlar and the full Prescribing Information for Mekinist.

Q: What can people do to try to prevent melanoma?

A: There are simple things you can do each day to help protect your skin. Here are a few:

• Wear protective clothing
• Apply broad-spectrum sunscreen SPF 15 or higher
• Avoid indoor or outdoor tanning
• Do a monthly skin self-examination
• Speak with your doctor about unusual marks or spots on the skin

Q: Where to go for more information?

A: Visit these web sites for additional information on melanoma, treatment and protecting the skin you’re in:

• tafinlarmekinist.com/advanced-melanoma/
• curemelanoma.org
• melanoma.org
• aimatmelanoma.org
• skincancer.org
• melanomainternational.org

What is Tafinlar + Mekinist
Tafinlar and Mekinist are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:

• That has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
• That has a certain type of abnormal “BRAF” (V600E or V600K mutation-positive) gene

Tafinlar and Mekinist are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal “BRAF” gene from coming back after the cancer has been removed by surgery.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal “BRAF V600E” gene.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):

• That has spread to other parts of the body and you have no satisfactory treatment options, and
• That has a certain type of abnormal “BRAF” gene

Tafinlar, in combination with Mekinist, should not be used to treat people with wild-type BRAF melanoma. Mekinist should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.

Your health care provider will perform a test to make sure that Tafinlar and Mekinist, in combination, are right for you.

It is not known if Tafinlar and Mekinist are safe and effective in children.

Important Safety Information

Tafinlar and Mekinist, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

When Tafinlar is used in combination with Mekinist, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like “coffee grounds,” or red or black stools that look like tar.

Mekinist, alone or in combination with Tafinlar, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider immediately if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.

Tafinlar, in combination with Mekinist, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

The combination of Tafinlar and Mekinist can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

Tafinlar, in combination with Mekinist, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

Tafinlar, in combination with Mekinist, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Fever is common during treatment with Tafinlar in combination with Mekinist, but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.

Rash and other skin reactions are common side effects of Tafinlar in combination with Mekinist. In some cases, these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.

Some people may develop high blood sugar or worsening diabetes during treatment with Tafinlar in combination with Mekinist. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.

Tafinlar may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.

Tafinlar, in combination with Mekinist, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.

Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with Tafinlar and Mekinist and for at least 4 months after the last dose of Tafinlar and Mekinist. For women of reproductive potential, Tafinlar and Mekinist, in combination, may harm your unborn baby. Use effective birth control (contraception) during treatment with Tafinlar and Mekinist in combination, and for 4 months after stopping treatment with Tafinlar and Mekinist. The most common side effects for patients with metastatic melanoma are: pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma receiving the combination as adjuvant therapy are: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.

Please see full Prescribing Information for Tafinlar at https://www.novartis.us/sites/www.novartis.us/files/tafinlar.pdf and Mekinist at https://www.novartis.us/sites/www.novartis.us/files/mekinist.pdf.

This content is sponsored by Novartis.