Dataset Information

Immune Checkpoint Inhibitor with or without Radiotherapy in Melanoma Patients with Brain Metastases: A Systematic Review and Meta-Analysis.

ABSTRACT:

Objective

Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis.

Materials and methods

A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes.

Results

Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44-61%); DCR, 57% (95% CI, 49-66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31-54%]; DCR, 85% [95% CI, 63-95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11-20%]; DCR, 26% [95% CI, 21-32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52-67%) compared to ICI monotherapy (11%; 95% CI, 8-17%) and ICI combined with radiotherapy (4%; 95% CI, 1-19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy).

Conclusion

ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

SUBMITTER: Kim PH

PROVIDER: S-EPMC8005357 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe development of brain metastases is common for systemic treatment failure in patients with melanoma and has been associated with a poor prognosis. Recent advances with BRAF and immune checkpoint therapies have led to improved patient survival. Herein, the authors evaluated the risk of de novo brain metastases and survival among patients with melanoma brain metastases (MBM) since the introduction of more effective therapies.MethodsPatients with unresectable AJCC stage III/IV melanoma who received first-line systemic therapy at Moffitt Cancer Center between 2000 and 2012 were identified. Data were collected regarding patient characteristics, stage of disease, systemic therapies, MBM status/management, and overall survival (OS). The risk of de novo MBM was calculated using a generalized estimating equation model and survival comparisons were performed using Kaplan-Meier and Cox proportional analyses.ResultsA total of 610 patients were included, 243 of whom were diagnosed with MBM (40%). Patients with MBM were younger, with a lower frequency of regional metastasis. No significant differences were noted with regard to sex, BRAF status, or therapeutic class. The risk of de novo MBM was found to be similar among patients treated with chemotherapy, biochemotherapy, BRAF-targeted therapy, ipilimumab, and anti-programmed cell death protein 1/programmed death-ligand 1 regimens. The median OS of patients with MBM was significantly shorter when determined from the time of first regional/distant metastasis but not when determined from the time of first systemic therapy. The median OS from the time of MBM diagnosis was 7.5 months, 8.5 months, and 22.7 months, respectively, for patients diagnosed from 2000 to 2008, 2009 to 2010, and 2011 to the time of last follow-up (P = .002).ConclusionsBrain metastases remain a common source of systemic treatment failure. The OS for patients with MBM has improved significantly. Further research into MBM prevention is needed. Cancer 2018;124:297-305. © 2017 American Cancer Society.