Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain
By H. Tawbi, P. Forsyth, A. Algazi, O. Hamid, S. Hodi, S. Moschos, N. Khushalani, K. Lewis, C. Lao, M. Postow and 12 more. New England Journal of Medicine, 2018
1,115 citations recorded by the source corpus.
BACKGROUND Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab inpatients with melanoma who had untreated brain metastases. METHODS In this open‐label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response. RESULTS Among 94 patients with a median follow‐up of 14.0 months, the rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56% (95% CI, 46 to 67). Treatment‐related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune‐related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases. CONCLUSIONS Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. (Funded by Bristol‐Myers Squibb and the National Cancer Institute; CheckMate 204 ClinicalTrials.gov number, NCT02320058.)
Subfields: Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/18673b16d9d74fd650f1e5637ed7fd3f1ac55136
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Citations in the corpus
- Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. (2019, background): “The outcomes are in favour of the combination with an overall response rate (ORR) of 46% in patients with asymptomatic BMs, reasonable response duration and PFS of more than 50% at 18 months [66, 85].”
- Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells (2020, background): “However, although they show some clinical efficacy in a subset of BrM patients (Hendriks et al., 2019; Long et al., 2018; Tawbi et al., 2018), ICB has only resulted in responses in isolated cases of primary gliomas to date (Lim et al.”
- Combination of CTLA-4 and PD-1 blockers for treatment of cancer (2019, neutral): “…benefit, 57%; Rate of extracranial clinical benefit, 56% 9-month PFS (global) rate, 57%; 9-month OS rate, 83 12-month OS rate, 82% Grade 3-4 AEs, 55% Tawbi et al 2018 Advanced melanoma Phase 2 NCT01783938 ≥ 15 months ORR, 56% Median OS, not reached 1-year OS rate, 76% Grade 3-5 AEs,…”