Introduction

Dabrafenib (trade name: Tafinlar) and trametinib (trade name: Mekinist) have been approved in Germany since 2013 and June 2014 respectively for the treatment of melanoma in adults that can't be surgically removed or that has already formed distant metastases. They have also been approved for use in combination with each other since 2015. Since August 2018, the combination has also been approved for use as supportive (adjuvant) therapy after surgery to remove melanoma that had spread to the lymph nodes. These medications – alone, or in combination with each other – are options for people who have a mutated protein in their tumor tissue (BRAF V600 mutation) that can lead to uncontrolled tumor growth.

Melanoma is the most dangerous type of skin cancer. It starts growing in the cells that produce the dark pigment in skin. Melanomas are usually surgically removed. But they are sometimes too large to be removed or may have spread to other parts of the body (metastatic tumors) through the blood or lymphatic system. If this happens, it is called advanced melanoma.

Dabrafenib aims to inhibit the mutated protein in order to prevent tumor growth, while trametinib blocks an alternative signal route, also stopping tumor growth.

Application

Dabrafenib is taken as a tablet (150 mg) every morning and evening, about one hour before or at least two hours after a meal. The two doses should be taken about 12 hours apart.

Trametinib is taken once a day as a tablet (2 mg).

The treatment is stopped if the disease progresses or if dangerous side effects arise. In adjuvant therapy, the treatment lasts twelve months. Here too, treatment is stopped if the disease comes back or if dangerous side effects arise.

Other treatments

At the time of the 2015 assessment, the drug vemurafenib was the standard treatment for adults who have melanoma that can't be removed surgically or has formed distant metastases.

After the complete surgical removal of melanoma with a BRAF V600 mutation and metastases in the lymph nodes, the standard treatment is watchful waiting: Patients are examined regularly in order to detect and treat any recurrence early on.

Assessment

In 2015, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether the combination of dabrafenib and trametinib, when compared with vemurafenib, has any advantages or disadvantages for people with advanced melanoma that can't be surgically removed or has formed distant metastases. The manufacturer provided one study for the purpose of this assessment.

In 2018, IQWiG looked into whether dabrafenib plus trametinib, when compared with watchful waiting, has any advantages or disadvantages for people who have had surgery to completely remove melanoma with a BRAF V600 mutation and lymph node metastases. Here, too, the manufacturer provided one study for the purpose of this assessment.

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More information

This information summarizes the main results of reviews produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The reviews were commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the reviews and the hearings received, the G-BA passed a resolution on the added benefit of dabrafenib (Tafinlar) and trametinib (Mekinist).