Outcomes of BRAF Mutated vs. Wild Type Tumors in Melanoma Brain Metastasis

Abstract

Purpose/Objective(s)Melanoma is the third most common cause of metastatic brain tumors. A mutation of the BRAF protein, a kinase implicated in cell differentiation and growth, is present in approximately 50% of patients with melanoma. BRAF inhibitors, such as Vemurafenib, have been used as treatment for BRAF mutant melanoma brain metastasis (MBM). BRAF mutations may impact patient outcomes in melanoma brain metastasis.Materials/MethodsPatients with Melanoma Brain Metastasis (MBM) and known BRAF mutation status treated at our tertiary care center (2010-2020) were evaluated. Overall Survival (OS) and Progression-Free Survival (PFS) were measured from diagnosis of MBM to date of death, progression, or last follow up. Many of these patients received multiple lines of treatment including targeted therapies at some point during their care. The Cox proportional hazard model was used to determine differences in OS and PFS.Results238 patients with MBM were included. Of these, 116 of which were of BRAF mutant and 122 were BRAF wild type status. For BRAF wild type patients the median age at diagnosis was 68 years (Interquartile range (IQR) 26-89), 70% of the patients were male, and 99% were white. For BRAF mutant patients the median age at diagnosis was 58 years (IQR 23-85), 63% of the patients were male, and 99% were white. Overall Survival for BRAF wild type and BRAF mutant patients had a median of 26.1 and 31.1 months and a 2 year rate of 64% and 51%, respectively. With BRAF wild type as a reference, BRAF mutant MBM patients had an OS hazard ratio, HR = 0.87 (95% CI = 0.64 – 1.17, P = 0.35). Progression-Free Survival for BRAF wild type and BRAF mutant patients had a median of 16.9 and 18.9 and a 2-year rate of 45% and 44%, respectively. With BRAF wild type as a reference, BRAF mutant MBM patients had an PFS hazard ratio, HR = 1.05 (95% CI = 0.79 – 1.39, P = 0.73).ConclusionBRAF mutation status alone does not have a significant effect on OS or PFS in patients with MBM. Further studies need to be done to determine effectiveness of treatments within each cohort, as well as to control for other patient variables such as KPS/ECOG, number of lesions, and extra-cranial metastasis. Melanoma is the third most common cause of metastatic brain tumors. A mutation of the BRAF protein, a kinase implicated in cell differentiation and growth, is present in approximately 50% of patients with melanoma. BRAF inhibitors, such as Vemurafenib, have been used as treatment for BRAF mutant melanoma brain metastasis (MBM). BRAF mutations may impact patient outcomes in melanoma brain metastasis. Patients with Melanoma Brain Metastasis (MBM) and known BRAF mutation status treated at our tertiary care center (2010-2020) were evaluated. Overall Survival (OS) and Progression-Free Survival (PFS) were measured from diagnosis of MBM to date of death, progression, or last follow up. Many of these patients received multiple lines of treatment including targeted therapies at some point during their care. The Cox proportional hazard model was used to determine differences in OS and PFS. 238 patients with MBM were included. Of these, 116 of which were of BRAF mutant and 122 were BRAF wild type status. For BRAF wild type patients the median age at diagnosis was 68 years (Interquartile range (IQR) 26-89), 70% of the patients were male, and 99% were white. For BRAF mutant patients the median age at diagnosis was 58 years (IQR 23-85), 63% of the patients were male, and 99% were white. Overall Survival for BRAF wild type and BRAF mutant patients had a median of 26.1 and 31.1 months and a 2 year rate of 64% and 51%, respectively. With BRAF wild type as a reference, BRAF mutant MBM patients had an OS hazard ratio, HR = 0.87 (95% CI = 0.64 – 1.17, P = 0.35). Progression-Free Survival for BRAF wild type and BRAF mutant patients had a median of 16.9 and 18.9 and a 2-year rate of 45% and 44%, respectively. With BRAF wild type as a reference, BRAF mutant MBM patients had an PFS hazard ratio, HR = 1.05 (95% CI = 0.79 – 1.39, P = 0.73). BRAF mutation status alone does not have a significant effect on OS or PFS in patients with MBM. Further studies need to be done to determine effectiveness of treatments within each cohort, as well as to control for other patient variables such as KPS/ECOG, number of lesions, and extra-cranial metastasis.