The Study: Despite the high prevalence, patients with melanoma brain metastases are often excluded from immunotherapy trials, leaving us with limited data on its efficacy in this scenario. This phase 2 Aussie trial randomized 63 patients with asymptomatic melanoma brain mets to nivo or combo nivo + ipi without radiation or surgery. The primary outcome of any intracranial response at 12 weeks was achieved in 20% with nivo alone and 46% with nivo+ipi. A complete response (CR) was observed in 12% and 17%, respectively. In the meantime, 76% of patients on nivo and 40% on nivo+ipi experienced intracranial progression. Not to mention over half had at least grade 3 toxicities with nivo+ipi, including 23% with severe colitis. Most remarkably, the blokes who authored this paper conclude combo nivo+ipi is now the preferred first-line therapy for asymptomatic melanoma brain mets. Ok. Now let’s put things in perspective. Immunotherapy is already standard of care for metastatic melanoma. Just like focal therapy for brain metastases, particularly in patients with excellent prognosis. But hey, we’re only basing this on prospective data on almost 1200 patients with up to 10 brain mets who achieved >90% local control at 6 months with radiosurgery. The at least grade 3 toxicity rate, you ask? That would be 32 of 1194, or <3%. Mic drop.
Bottom Line: Nivo+ipi has a 46% intracranial response rate at 12 weeks for asymptomatic melanoma brain mets, which is surpassed by the grade 3 or higher toxicity rate. Beam on. | Long, Lancet Oncol 2018