Central Nervous System
PV QA 2 - Poster Viewing Q&A 2
Purpose/Objective(s):Retrospective evaluation of overall survival (OS) and cause-specific survival (CSS) in melanoma brain metastasis (MBM) patients who received stereotactic radiosurgery (SRS) with or without immunotherapy.
Materials/Methods:A retrospective analysis was performed on 68 MBM patients with 229 total lesions treated with SRS between 2008 to 2017. Patients with at least one brain CT/MRI following SRS were included in the evaluation . Date of initial SRS was the starting point for OS and CSS outcomes. CSS death events were defined as neurologic death events. Survival analysis was performed using Kaplan-Meier estimates and Cox regression. Covariates for multivariate analysis (MVA) included gender, age, number of SRS-treated lesions, KPS, extra-cranial metastasis status and extracranial disease activity, BRAF status, WBRT history, and sequence of immunotherapy with SRS. The immunotherapy agents of interest in this study were ipilimumab, nivolumab, and pembrolizumab.
Results:The median follow-up for our study was 35.35 months. Median OS was 6.43 months (95% CI 3.07-9.80) while median CSS was 10.00 months (95% CI 5.84-14.15) for our cohort. Forty-nine (72.06%) patients received immune checkpoint inhibitors. Fifteen (22.06%) patients received PD-1 inhibitors (nivolumab, pembrolizumab) and 47 (69.12%) patients received ipilimumab. Treatment with SRS and immune checkpoint inhibitors was associated with superior OS (HR 0.48, 95% CI 0.27-0.85, p=0.01). Patients receiving immunotherapy had a median OS of 8.65 months (95% CI 4.48-12.81) and a median CSS of 25.49 (95% CI 3.71-47.27) months versus 3.29 months (95% 2.55-4.02) and 4.50 months (95% CI 1.46-7.55), respectively, for the non-immunotherapy cohort. MVA confirmed an OS benefit for both ipilimumab (HR 0.25, 95% CI 0.10-0.67, p<0.01) and PD-1 inhibitors (HR 0.09, 95% CI 0.03-0.30, p<0.01). On univariate analysis, PD-1 inhibitor patients had significantly longer CSS when compared to non-immunotherapy patients (HR 0.22, 95% CI 0.75-0.67, p=0.01). On MVA, there was a trend towards CSS benefit for both ipilimumab (HR 0.27, 95% CI 0.05-1.60, p=0.15) and PD-1 inhibitors (HR 0.12, 95% CI 0.01-1.21, p=0.07). Patients who received ipilimumab but no PD-1 inhibitors had a median OS of 6.43 months (95% CI 2.86-10.00) and a median CSS of 14.29 months (95% CI 7.10-21.48). Those who received PD-1 inhibitors had a median OS of 23.51 months (95% CI 5.15-41.87). The PD-1 inhibitor cohort did not reach median CSS, however, the median follow-up for censored patients was 28.38 months. No other covariates were significantly associated with either OS or CSS.
Conclusion:Our retrospective cohort of melanoma brain metastasis patients treated with immunotherapy and stereotactic radiosurgery have significantly improved overall and cause-specific survival than those treated without immunotherapy. The effect on OS and CSS is greater with PD-1 immune checkpoint inhibitors.
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