Nivolumab plus ipilimumab in melanoma brain metastases.

Abstract

About 25–30% of patients with stage IV melanoma manifest clinically apparent melanoma brain metastases at some point in their disease course. 1 Davies MA Saiag P Robert C et al. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017; 18: 863-873 Google Scholar Until approximately 10 years ago, few patients with melanoma brain metastases were eligible for clinical trials and survival rates were very poor, with a median survival generally being 3–5 months. 2 Davies MA Liu P McIntyre S et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer. 2011; 117: 1687-1696 Google Scholar In The Lancet Oncology, Hussein Tawbi and colleagues 3 Tawbi HA Forsyth PA Hodi FS et al. Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. Lancet Oncol. 2021; 22: 1692-1704 Google Scholar report the long-term results of the CheckMate 204, an open-label, multicentre, phase 2 study assessing the efficacy of the combination of nivolumab plus ipilimumab in patients with active melanoma brain metastases. Interestingly, these results show that the objective intracranial response to nivolumab plus ipilimumab might be similar to the extracranial response; Tawbi and colleagues conclude that the durable 3-year response, overall survival, and progression-free survival rates for asymptomatic patients support first-line use of nivolumab plus ipilimumab. Nivolumab plus ipilimumab in melanoma brain metastasesIn their Article in The Lancet Oncology, Hussein Tawbi and colleagues1 report a remarkable 71·9% 3-year overall survival rate for patients with melanoma and asymptomatic brain metastases treated with nivolumab plus ipilimumab in the CheckMate 204 trial. These findings strongly support the activity of the nivolumab plus ipilimumab combination, recently reported in the same clinical setting by the anti-PD-1 brain collaboration (ABC) study,2 in which the 5-year survival rate was 51%, and by the Italian Network for Tumor Biotherapy-Melanoma 2 (NIBIT-M2) study,3 in which the 5-year survival rate was 41%. Full-Text PDF Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 studyThe durable 3-year response, overall survival, and progression-free survival rates for asymptomatic patients support first-line use of nivolumab plus ipilimumab. Symptomatic disease in patients with MBM remains difficult to treat, but some patients achieve a long-term response with the combination. Full-Text PDF Nivolumab plus ipilimumab in melanoma brain metastases – Authors' replyWe thank Alessandro Rizzo for his recognition of our work as well conducted and agree with careful application of our results in clinical practice. In our study,1 more than half the patients with asymptomatic melanoma brain metastases had intracranial responses with the combination of nivolumab plus ipilimumab, the median time to response was 6 weeks. Additionally, more than 85% of responses were durable at 3 years, indicating no further need for stereotactic radiosurgery. We strongly advocate for multidisciplinary review of individual cases with radio-oncologists, neurosurgeons, medical oncologists, and radiologists to determine the safety of deferring local therapy for approximately 6 weeks to allow systemic therapy to exert its effect. Full-Text PDF