Brain Metastases in Metastatic Cutaneous Melanoma: Patterns of Care and Clinical Outcomes in the Era of Immunotherapy and Targeted Therapy.

Purpose/Objective(s) Immune checkpoint inhibitors (CPIs) and BRAF inhibitors (BIs) are standard treatments for metastatic melanoma and have intracranial activity against melanoma brain metastases (MBMs). However, optimal use of CPI/BI with radiation therapy (RT) is not well established. This study evaluates the current practice pattern of how these systemic therapies are chosen and combined with either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for MBMs. The study also examines if upfront SRS+CPI results in superior intracranial control (IC) than upfront SRS without CPI or upfront CPI/BI followed by salvage RT. Materials/Methods Patients with MBMs who received their first course of intracranial RT with between 1/2014 and 12/2019 at a tertiary cancer center were retrospectively reviewed. Patients with leptomeningeal disease and MBMs from non-cutaneous melanoma were excluded. Prior exposure before MBM diagnosis and concomitant use of CPIs/BIs within 3 months of RT were evaluated. Binary logistic regression was performed to determine predictors of SRS or CPI use. Cox regression analysis was used to assess the association with IC, which was calculated from the time of MBM diagnosis to the first intracranial progression after upfront MBM treatment. Results A total of 123 patients with MBMs with a median age of 61 (IQR: 51-69) were identified, and 55% were BRAF-mutant. There were 75 patients (61%) with 1-4 MBMs, 31 patients (25%) with 5-10 MBMs, and 17 (14%) patients with > 10 MBMs. Before MBM diagnosis, 30% had prior CPI and 18% had prior BI. For the upfront MBM treatment, 64% received SRS (66% with CPI and 23% with BI), 27% received WBRT (42% with CPI and 30% with BI), 9% received upfront CPI/BI. The baseline characteristics were balanced between the patients who received upfront SRS and upfront CPI/BI except patients who received upfront CPI/BI were more likely to have a BRAF mutation (82% vs. 49%, P = 0.04). The median follow-up was 8.7 mo (IQR: 2.8-22) for all patients and 32 mo (IQR: 18-45) for living patients. For patients who received upfront CPI/BI, 73% underwent salvage SRS and 27% with salvage WBRT at a median of 5.7 mos [IQR: 3.0-7.7] after MBM diagnosis. Fewer number of MBMs, higher KPS, and craniotomy were significant predictors of SRS use on multivariable logistic regression. For the upfront SRS cohort, treatment after 2016, BRAF-wild type status, and prior CPI exposure were associated with higher likelihood of concomitant CPI use with SRS. After adjusting for the number of MBMs, upfront SRS+CPI was associated with higher IC than upfront SRS without CPI (HR: 0.43, 95% CI: 0.22-0.84, P = 0.02). Upfront SRS+ CPI also trended towards a higher IC than upfront CPI/BI with salvage RT (HR: 0.54, 95% CI: 0.27-1.1, P = 0.07) after adjusting for the number of MBMs. Conclusion Upfront SRS with concomitant CPI was the most frequently used approach to treat newly diagnosed favorable MBMs and may yield superior IC than upfront SRS without CPI or upfront CPI/BI. Author Disclosure R. Chin: None. K. Chen: None. C.D. Abraham: None. C.G. Robinson: Research Grant; Varian. Consultant; Varian, AstraZeneca, EMD Serono. Advisory Board; Radialogica. Stock Options; Radialogica. S.M. Perkins: I serve on the Medical Advisory Committee for Mevion Medical Systems and receive compensation for this role.; Mevion Medical Systems. T.M. Johanns: None. L.F. Hernandez-Aya: None. J.W. Keller: None. J. Dowling: None. K. Rich: None. M. Chicoine: None. A.H. Kim: None. G.P. Dunn: None. G. Ansstas: None. J. Huang: None.