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

Abstract 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; P < .001), more symptomatic MBMs (59.4% vs 11.1%; P < .001), higher rates of upfront craniotomy (47.8% vs 7.9%; P < .001), and fewer BRAF V600 mutations (34.8% vs 54.0%; P = .035). Upfront cSRS was not associated with longer overall survival (median 47.0 mo vs not reached; aHR = 1.01 [95% CI, 0.60-1.68]; P = .98) but was associated with reduced incidence of intracranial progression (median 37.6 vs 5.5 mo; aHR = 0.40 [95% CI, 0.25-0.64]; P < .001). 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.