Current Treatment of Melanoma Brain Metastases

Abstract

Melanoma is a type of skin cancer in which there is a strong correlation between its occurrence and exposure to ultraviolet radiation. Although it is not the most common skin cancer, it has the highest mortality rate of all skin cancers. The prognosis of patients is significantly worsened by melanoma metastasis to the brain, which often occurs in patients with advanced disease. The formation and development of melanoma metastases to the brain involve a very complex process, and their mechanisms are not fully understood. One of the ways for metastatic melanoma cells to survive and develop cancer in the brain environment is the presence of oncogenic BRAF mutation, which occurs in up to 50% of metastatic melanoma cases. Before discovering new methods of treating metastases, the overall survival of patients with this disease was 6 months. Currently, research is being conducted on new drugs using immunotherapy (immune checkpoint inhibitors: anti-PD-1, anti-CTLA-4) and targeted therapy (BRAF and MEK inhibitors) to improve the prognosis of patients. In this article, we summarize the current state of knowledge about the results of treating brain metastases with new systemic therapies.

Immunotherapy Combined with Radiation in Malignant Melanoma without BRAF Mutations Brain Metastases—Favorable Response after Immunotherapy Continued beyond Progression

“…Many studies have shown that combination therapy (anti-CTLA-4 + anti-PD-1) increases the response rates compared to monotherapy [3,4]. Some studies did not reveal differences between the survival of patients with negative BRAF malignant melanoma with brain metastases who underwent double immunotherapy (CTLA-4 + PD-1), compared to those who underwent immunotherapy with one agent PD-1 [20].…”

“…As a systemic treatment, immunotherapy is the primary option for malignant melanoma patients with brain metastases in the absence of the V600 mutation of the BRAF gene, being a safe therapeutic option [3].…”

Exploring Immune-Related Adverse Events: A Case of Febrile Neutropenia in a Melanoma Patient Receiving Immunotherapy

“…The first encompasses the use of ICIs, targeting CTLA-4 and PD-1. The second approach includes drugs targeting key protein kinases involved in melanoma pathogenesis, such as BRAF and MEK [9,10].…”

Personalized identification and characterization of genome-wide gene expression differences between patient-matched intracranial and extracranial melanoma metastasis pairs

“…For patients with intracranial metastases, the treatment response duration of BRAF/MEK inhibitors is only limited to a few months and the efficacy of immune checkpoint inhibitors is substantially reduced in symptomatic patients [1,[4][5][6][7][8]. Results of important clinical immunotherapy trials for melanoma patients with intracranial metastases are summarized in [9]. Clinical outcomes of melanoma patients with intracranial metastases treated with stereotactic radiosurgery and various systemic therapies have been analyzed in [10].…”