A review of melanoma brain metastasis

This study investigated the clinical features and outcomes of brain metastases in melanoma (MBM). Researchers reported that to improve outcomes for melanoma patients with brain metastasis, both clinical and pre-clinical efforts are necessary. This will include studying the brain tumor environment and associated treatment toxicities.

Melanoma has the highest risk of spread to the brain among all common cancer types. Previous studies have reported that 40-60% of patients with metastatic melanoma develop MBM at some point in the disease course. Limited studies are available that have included patients with MBM. Improving outcomes for these patients will involve understanding the tumor biology and the treatment associated toxicities and resistance. 

The objective of this review was to provide information about the current status of the field of MBM research. This review also identifies important features for improving patient outcomes and gives suggestions on how to improve future research in this area.  

Temozolomide (Temodar) is the chemotherapy agent that has been frequently used in MBM patients, despite having response rates of only 3-7%. Targeted therapies have been described to have much better results in these patients.

Some melanoma patients have a mutation (permanent change) in the BRAF gene. Targeted therapy such as BRAF inhibitors (dabrafenib or vemurafenib) are effective in these patients. In a previous study including 172 patients with a BRAF mutation and MBM, dabarafenib led to a disease control rate of 81.1%.

While BRAF inhibitors can be very effective, some patients become resistant to this type of treatment. This occurs due to the reactivation of the MAPK pathway (another protein involved in cancer growth). Adding an MAPK inhibitor to the treatment helps to overcome this resistance. Combining BRAF and MAPK therapy has been shown to be even more beneficial than BRAF inhibitors alone. However, progression-free survival is short in patients treated with MAPK inhibitors. This may be due to particular factors in the MBM not present in the main tumor.

Immune therapy has also been shown to benefit MBM patients. Immune therapies such as ipilimumab (Yervoy) and pembrolizumab (Keytruda) are treatments that stimulate the immune system to attack tumor cells. A study with ipilimumab in patients with advanced melanoma showed that 5 out of 12 patients responded to the treatment. Another study with 72 patients showed an MBM disease control rate of 24% and a 1-year overall survival of 20%. A study with pembrolizumab is also ongoing and so far 22% of patients had MBM disease response, 3 had stable disease (no increase or decrease in tumor size) and 7 had disease progression.

Brain surgery for MBM results in better disease control and improved outcomes than radiation therapy. However, the combined treatment of surgery with radiation leads to better results than surgery alone. Radiation therapy alone fails to provide prolonged results, as most patients experience recurrent brain metastasis. Radiosurgery has become a highly effective local therapy for MBM, and the standard treatment for patients with limited MBM. Previous studies showed a 1-year MBM disease control of more than 80% and an average overall survival of 5-11 months.

The clinical management of patients with MBM requires collaborations with teams of doctors from different fields. This would help making treatment decisions and to evaluate and manage treatment response and complications. Moreover, collaborations with physicians working on other type of brain cancers would also help to understand the disease and develop more effective therapies.

This study reviewed the current status of the MBM field, identified features for improving outcomes in patients with MBM and suggested in how to improve future research in this area.