Outcomes of patients with melanoma brain metastases treated with ipilimumab and nivolumab with or without upfront comprehensive stereotactic radiosurgery.

Background: The efficacy of ipilimumab and nivolumab (ipi/nivo) for melanoma brain metastases (MBMs) has been previously reported, leading to uncertainty regarding the optimal role of comprehensive stereotactic radiosurgery (cSRS). We therefore conducted a single-institution retrospective study to compare outcomes of upfront versus deferred cSRS for MBM treated with ipi/nivo. Methods: We identified patients who started ipi/nivo for newly diagnosed MBMs between 2018 and 2023, with or without upfront cSRS. Patients with >15 MBMs, leptomeningeal disease, or whole-brain radiotherapy at baseline were excluded. Outcomes were compared using multivariable regression and reported as adjusted hazard ratios (aHRs) with 95% CIs. Results: Of the 132 patients identified, 52.3% received upfront cSRS and 47.7% did not. Patients who received upfront cSRS had larger maximum MBMs (median 2.3 vs 0.7 cm; Conclusions: In this retrospective study, upfront cSRS was more often used in patients with higher-risk MBM and was associated with improved intracranial control, although no significant survival benefit was observed. These findings suggest that starting ipi/nivo alone may be reasonable for lower-risk MBM, but prospective studies are needed to guide optimal integration of cSRS.