Introduction

The combination of the drugs binimetinib (trade name: Mektovi) and encorafenib (trade name: Braftovi) has been approved in Germany since September 2018 for the treatment of melanoma in adults if surgery is no longer possible or if the cancer has already spread to other parts of the body (metastasis). The combination is suitable 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.

Encorafenib aims to inhibit this mutated protein and stop tumor growth, while binimetinib blocks an alternative signal route, thereby preventing tumor growth too.

Application

Binimetinib is taken as a capsule. One capsule contains 15 mg. The daily dose is 45 mg in the morning and 45 mg in the evening. The doses should be taken about 12 hours apart.

Encorafenib is taken once a day as a capsule. One capsule contains 75 mg. The daily dose is 450 mg when used in combination with binimetinib.

Other treatments

The standard treatment for patients who have advanced melanoma and the BRAF V600 mutation, and who have already received treatment, depends on things like which medication has already been used. The treatment is individually adjusted by the doctor.

The standard treatment for patients who haven't yet received treatment is a combination of vemurafenib and cobimetinib or dabrafenib and trametinib.

Assessment

In 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether the combination of binimetinib and encorafenib has any advantages or disadvantages compared with the standard treatments for people who have advanced melanoma and the BRAF V600 mutation.

The manufacturer didn't provide any suitable data regarding patients who have already received treatment. So it remains unclear whether the combination of binimetinib and encorafenib has any advantages or disadvantages compared with the standard treatment for patients who have already received treatment.

The manufacturer provided data suitable for an indirect comparison in patients who haven't yet received treatment.

In scientific research, a direct comparison is a comparison made between two medications in a single study. Half of the participants in the study are given medication A, and the other half receive the standard treatment. After the study is completed, the number of certain events in each group – such as deaths, occurrences of symptoms or side effects – are compared.

Indirect comparisons, on the other hand, involve two different studies (in the simplest case): One study compares medication A with medication X. The other compares medication X with the standard treatment. Then the results for medication A from the first study are compared with the results for the standard treatment from the second study. The results of this kind of comparison are generally less reliable than a direct comparison.

In this case, one study compared binimetinib plus encorafenib with vemurafenib, and the other compared vemurafenib with the standard treatment of vemurafenib plus cobimetinib.

What advantages or disadvantages does binimetinib plus encorafenib have?

The combination of binimetinib plus encorafenib wasn't found to have any advantages or disadvantages compared to the standard treatment of vemurafenib plus cobimetinib.

No differences

Life expectancy: There was no difference between binimetinib plus encorafenib and the standard treatment here.

What remains unanswered?

The manufacturer did not provide any suitable data concerning:

  • symptoms of the disease
  • general health
  • quality of life
  • severe side effects
  • treatment stopped due to severe side effects

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 binimetinib (trade name: Mektovi) and encorafenib (trade name: Braftovi).