Clinical Outcomes and Toxicity After Combination Stereotactic Radiosurgery and Ipilimumab in Patients With Melanoma Brain Metastases

Abstract

Purpose: There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases. Methods: We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006-2015. Concurrent ipilimumab administration was defined as within +/- 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan-Meier method. OS was analyzed with Cox regression. Results: Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p=0.02). In multivariate analysis, ipilimumab (p=0.05), diagnosis-specific graded prognostic assessment (p=0.02), and number of brain metastases (p=0.05) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. Most radiation necrosis events occurred in patients who received ipilimumab. Conclusions: Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.