P14.29 The treatment of melanoma brain metastases with stereotactic radiosurgery concurrently with immune checkpoint inhibition is associated with improved extracranial disease control and overall survival compared to the overall metastatic melanoma cohort - a synergistic effect reaching beyond local control?
Authors: Webb P S , Zorman M , Watson R , Payne M , Coupe N , Hobbs C 
Published: September 2021

Abstract

BACKGROUND
Melanoma brain metastases (MBM) are an increasingly common referral to the neuro-oncology MDT in the context of lengthening survivorship of metastatic melanoma (MM) patients in the immunotherapy era. Stereotactic radiosurgery (SRS) and immune checkpoint inhibition (ICI) are both effective in the management of MBM and, when combined, 12-month local control rates of &gt;85% and overall survival (OS) &gt;80% have been reported.[4,5] Recent local analysis of patients treated at our tertiary SRS referral centre has revealed even greater outcomes in this patient cohort. This study aimed to compare the outcomes of patients with MBM treated with concurrent SRS and ICI compared to the overall metastatic melanoma cohort, to elucidate whether the addition of SRS to ICI may improve disease control outside of the brain as well as within.

MATERIAL AND METHODS
A retrospective analysis of our local SRS database and an ARIA ePrescribing database search was performed to identify a cohort of patients treated with concurrent SRS and ICI for MBM, as well as a control cohort of MM patients who received ICI alone, over a 4 year period until February 2020. The primary endpoints were the extracranial progression free survival (PFS) and overall survival (OS) at 12 months. Secondary endpoints were the median PFS (mPFS) and OS (mOS). Kaplan-Meier curves and survival statistics were generated using SPSS v26.

RESULTS
A total of 34 MBM from 19 patients were identified in the SRS+ICI group and there were 200 patients in the control group. The minimum follow up was 12 months. The median patient age, duration of ICI and use of combination ICI favoured the SRS+ICI group. The number of sites of extracranial disease pre-ICI and overall anti-PD-1 usage was well matched. In the SRS+ICI group, there were no cases of extracranial progression and no deaths within 12 months. In the control group, the 12-month PFS and OS rates were 50.5% and 77.5% respectively. In terms of mPFS, this was not reached (estimated 37.6 months) in the SRS+ICI group, versus 13.4 months in the control group (log rank test, p=0.001). In terms of mOS, this was not reached in the SRS+ICI group, versus 55.8 months in the control group (log rank test, p=0.016).

CONCLUSION
We demonstrate improved extracranial disease control and survivorship amongst metastatic melanoma patients who develop brain metastases and are treated with concurrent SRS and ICI compared to those who do not. The outcomes of our control cohort are comparable to the 4-year follow up of the CheckMate 067 trial (n=945),[6] which strengthens the validity of the statistical comparisons made in this study. The improved extracranial disease control seen when SRS and ICI are combined in the treatment of MBM questions whether an abscopal effect may be at play, and therefore further accents the utility of SRS in MBM beyond that of local control alone. This could influence management in cases of borderline decisions for SRS.