Dataset Information

SRS in Combination With Ipilimumab: A Promising New Dimension for Treating Melanoma Brain Metastases.

ABSTRACT: Stereotactic radiosurgery provides effective local control, but high recurrence rate are observed while ipilimumab have shown promising improvements in survival in the treatment of melanoma brain metastases. This meta-analysis was done to review the clinical evidence regarding the combination of stereotactic radiosurgery and ipilimumab in the treatment of brain metastases from melanoma. Comprehensive research of the electronic databases (PubMed and Cochrane Library) was carried out in April 2017. Different combination of MESH headings and words were used. Review Manager was used to analyze the outcome data of interest. According to heterogeneity, fixed effects model or random effects model was adapted. Six retrospective studies comparing stereotactic radiosurgery plus ipilimumab with stereotactic radiosurgery alone were found. Total of 411 participants were included in this meta-analysis. Of that, 128 patients had received stereotactic radiosurgery + ipilimumab, while 283 patients had received stereotactic radiosurgery only. Stereotactic radiosurgery plus ipilimumab significantly improved survival when compared to stereotactic radiosurgery alone (hazard ratio: 0.74 [95% confidence interval: 0.56-0.99, P = .04]), with no significant increase in the incidence of adverse events (odds ratio 0.57 [95% confidence interval: 0.28-1.17, P = .12]). Stereotactic radiosurgery with ipilimumab is safe and effective treatment option and can be recommended for the treatment of brain metastases in patients with melanoma.

SUBMITTER: Khan M

PROVIDER: S-EPMC6137552 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SRS in Combination With Ipilimumab: A Promising New Dimension for Treating Melanoma Brain Metastases.

Khan Muhammad M Lin Jie J Liao Guixiang G Tian Yunhong Y Liang Yingying Y Li Rong R Liu Mengzhong M Yuan Yawei Y

Technology in cancer research & treatment 20180101

Stereotactic radiosurgery provides effective local control, but high recurrence rate are observed while ipilimumab have shown promising improvements in survival in the treatment of melanoma brain metastases. This meta-analysis was done to review the clinical evidence regarding the combination of stereotactic radiosurgery and ipilimumab in the treatment of brain metastases from melanoma. Comprehensive research of the electronic databases (PubMed and Cochrane Library) was carried out in April 2017 ...[more]

PMID: 30213236

Similar Datasets

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.

Project description:BackgroundCombination nivolumab plus ipilimumab was efficacious in patients with asymptomatic melanoma brain metastases (MBM) in CheckMate 204, but showed low efficacy in patients with symptomatic MBM. Here, we provide final 3-year follow-up data from the trial.MethodsThis open-label, multicentre, phase 2 study (CheckMate 204) included adults (aged ≥18 years) with measurable MBM (0·5-3·0 cm in diameter). Asymptomatic patients (cohort A) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and no neurological symptoms or baseline corticosteroid use; symptomatic patients (cohort B) had an ECOG performance status of 0-2 with stable neurological symptoms and could be receiving low-dose dexamethasone. Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg was given intravenously every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks for up to 2 years, until disease progression or unacceptable toxicity. The primary endpoint was intracranial clinical benefit rate (complete responses, partial responses, or stable disease lasting ≥6 months) assessed in all treated patients. Intracranial progression-free survival and overall survival were key secondary endpoints. This study is registered with ClinicalTrials.gov, NCT02320058.FindingsBetween Feb 19, 2015, and Nov 1, 2017, 119 (72%) of 165 screened patients were enrolled and treated: 101 patients were asymptomatic (cohort A; median follow-up 34·3 months [IQR 14·7-36·4]) and 18 were symptomatic (cohort B; median follow-up 7·5 months [1·2-35·2]). Investigator-assessed intracranial clinical benefit was observed in 58 (57·4% [95% CI 47·2-67·2]) of 101 patients in cohort A and three (16·7% [3·6-41·4]) of 18 patients in cohort B; investigator-assessed objective response was observed in 54 (53·5% [43·3-63·5]) patients in cohort A and three (16·7% [3·6-41·4]) patients in cohort B. 33 (33%) patients in cohort A and three (17%) patients in cohort B had an investigator-assessed intracranial complete response. For patients in cohort A, 36-month intracranial progression-free survival was 54·1% (95% CI 42·7-64·1) and overall survival was 71·9% (61·8-79·8). For patients in cohort B, 36-month intracranial progression-free survival was 18·9% (95% CI 4·6-40·5) and overall survival was 36·6% (14·0-59·8). The most common grade 3-4 treatment-related adverse events (TRAEs) were increased alanine aminotransferase and aspartate aminotransferase (15 [15%] of 101 patients each) in cohort A; no grade 3 TRAEs occurred in more than one patient each in cohort B, and no grade 4 events occurred. The most common serious TRAEs were colitis, diarrhoea, hypophysitis, and increased alanine aminotransferase (five [5%] of each among the 101 patients in cohort A); no serious TRAE occurred in more than one patient each in cohort B. There was one treatment-related death (myocarditis in cohort A).InterpretationThe 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.FundingBristol Myers Squibb.

Dataset Information

SRS in Combination With Ipilimumab: A Promising New Dimension for Treating Melanoma Brain Metastases.

Publications

SRS in Combination With Ipilimumab: A Promising New Dimension for Treating Melanoma Brain Metastases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets