Treatment options for melanoma with brain metastasis

The authors reviewed different treatment options for melanoma that spread to brain. This included surgery and combination treatment, among others, and scope for future treatments. 

In advanced melanoma, the cancer often spreads to the brain. This is called brain metastasis. This affects quality of life and also shortens the life span of patients. The traditional treatments for brain metastasis in melanoma have been surgery and radiotherapy. Radiotherapy is directing a beam of radiation to the tumor site to kill cancer cells. Immunotherapy and targeted therapy are newer and promising treatment options for this disease. Immunotherapy uses the body’s own immune system to fight cancer. Targeted therapy attacks specific genes, which are often changed (mutated) in melanoma patients. 

The authors aimed to review different treatment options for melanoma with brain metastasis.

Local treatment

The choice of local treatment (at the site of brain metastasis) depends on the number of brain tumors, patient well-being, and extent of disease spread outside the brain. Based on several studies, the average overall survival (patients still alive after treatment) was roughly 2–3 months for untreated melanoma brain metastases. It was 2–5 months with radiotherapy for whole brain. It was 8–11 months with surgery or stereotactic radiosurgery (SRS, a type of surgery). It was 13–14 months with combination of these local treatments.

Immunotherapy

Ipilimumab (Yervoy) is an approved and standard immunotherapy for melanoma with brain metastasis. In two international phase 3 trials, 42 previously treated and 43 untreated patients were given ipilimumab or standard care of treatment. These trials showed significant improvement in overall survival with ipilimumab. Clinical benefits were observed in patients with brain metastasis treated with ipilimumab compared to those who were not. Benefits in survival were seen in patients who were not showing symptoms of their brain metastases compared to those who were symptomatic.

Other immunotherapies such as nivolumab (Opdivo) and pembrolizumab (Keytruda) have also shown great promise in patients with metastatic melanoma. These could be used both as single agents and in combination with ipilimumab.

BRAF inhibitors

In the majority of metastatic melanoma patients, BRAF genes are mutated. These genes are involved in cellular signaling and functioning of important proteins. BRAF inhibitors, such as dabrafenib (Tafinlar), are targeted therapies that block certain cell signaling proteins (e.g. MAPK and MEK) in melanoma cells containing mutated BRAF genes. In one study, 9 out of 10 patients with BRAF mutation treated with dabrafenib achieved either complete or partial disappearance of tumor (response). 4 of these patients had complete disappearance of tumor.

Trametinib (Mekinist), an oral MEK inhibitor, also showed promise in treating brain metastasis. In a phase 3 trial of trametinib in BRAF-mutant metastatic melanoma patients, 22% showed a response to treatment. Progression-free survival (PFS, time from treatment until disease progression) was 4.8 months. 81% of patients survived for at least 6 months.

The authors concluded that the most beneficial treatment depends on the extent and mutation status of the patient. Surgery and SRS could be the preferred treatment for patients with limited brain metastasis. For patients with BRAF mutation, BRAF inhibitors would be preferred over radiotherapy.