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Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases.

ABSTRACT: Melanoma is an aggressive malignancy with a deplorable penchant for spreading to the brain. While focal therapies such as surgery and stereotactic radiosurgery can help provide local control, the majority of patients still develop intracranial progression. Novel therapeutic combinations to improve outcomes for melanoma brain metastases (MBM) are clearly needed. Ipilimumab, the anticytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, has been shown to improve survival in patients with metastatic melanoma, but many of these trials either excluded or had very few patients with MBM. This article will review the efficacy and limitations of ipilimumab therapy for MBM, describe the current evidence for combining ipilimumab with radiation therapy, illustrate potential mechanisms for synergy, and discuss emerging clinical trials specifically investigating this combination in MBM.

SUBMITTER: Patel KR

PROVIDER: S-EPMC4578585 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases.

Patel Kirtesh R KR Lawson David H DH Kudchadkar Ragini R RR Carthon Bradley C BC Oliver Daniel E DE Okwan-Duodu Derick D Ahmed Rafi R Khan Mohammad K MK

Neuro-oncology 20150525 10

Melanoma is an aggressive malignancy with a deplorable penchant for spreading to the brain. While focal therapies such as surgery and stereotactic radiosurgery can help provide local control, the majority of patients still develop intracranial progression. Novel therapeutic combinations to improve outcomes for melanoma brain metastases (MBM) are clearly needed. Ipilimumab, the anticytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, has been shown to improve survival in patients with ...[more]

PMID: 26014049

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Project description:PurposeTo investigate the efficacy and safety of concurrent stereotactic radiosurgery (SRS) and ipilimumab or nivolumab in patients with untreated melanoma brain metastases.Patients and methodsEighty consecutive patients with 326 melanoma brain metastases receiving SRS in combination with ipilimumab or nivolumab were identified from an institutional database and retrospectively evaluated. Patients started systemic treatment with intravenous nivolumab or ipilimumab within one week of receiving SRS. Nivolumab was given at doses of 3 mg/kg every two weeks. Ipilimumab was administered up to four doses of 10 mg/kg, one every 3 weeks, then patients had a maintenance dose of 10 mg/kg every 12 weeks, until disease progression or inacceptable toxicity. Primary endpoint of the study was intracranial progression-free survival (PFS). Secondary endpoints were extracranial PFS, overall survival (OS), and neurological toxicity.ResultsEighty patients were analyzed. Forty-five patients received SRS and ipilimumab, and 35 patients received SRS and nivolumab. With a median follow-up of 15 months, the 6-month and 12-month intracranial PFS rates were 69% (95%CI,54-87%) and 42% (95%CI,24-65%) for patients receiving SRS and nivolumab and 48% (95%CI,34-64%) and 17% (95%CI,5-31%) for those treated with SRS and ipilimumab (p = 0.02), respectively. Extracranial PFS and OS were 37 and 78% in SRS and nivolumab group, respectively, and 17 and 68% in SRS and ipilimumab group, respectively, at 12 months. Sub-group analysis showed significantly better intracranial PFS for patients receiving multi-fraction SRS (3 × 9 Gy) compared to single-fraction SRS (70% versus 46% at 6 months, p = 0.01), especially in combination with nivolumab. Grade 3 treatment-related adverse events occurred in 11 (24%) patients treated with SRS and ipilimumab and 6 (17%) patients who received SRS and nivolumab. Radiation-induced brain necrosis (RN) occurred in 15% of patients.ConclusionsConcurrent SRS and ipilimumab or nivolumab show meaningful intracranial activity in patients with either asymptomatic and symptomatic melanoma brain metastases, although a subset of patients may develop symptomatic RN. The combination of nivolumab with SRS is associated with better intracranial control.

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Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases.

Publications

Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases.

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