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Heppt, Markus V.; Steeb, Theresa; Schlager, Justin Gabriel; Rosumeck, Stefanie; Dressler, Corinna; Ruzicka, Thomas; Nast, Alexander and Berking, Carola (2017): Immune checkpoint blockade for unresectable or metastatic uveal melanoma: A systematic review. In: Cancer Treatment Reviews, Vol. 60: pp. 44-52

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Abstract

Background: The use of immune checkpoint blockade (ICB) for uveal melanoma (UM) is little established. The aim of this review was to provide a comprehensive overview on the efficacy, safety, and tolerability of ICB in patients with UM. Methods: We performed a systematic literature research covering MEDLINE, Embase and CENTRAL. Abstracts of pertinent conferences and trial registers were handsearched for relevant studies. Results: Out of 1327 records initially identified, 12 eligible studies were included in the qualitative synthesis. They comprised 7 expanded access or named patient programs (n = 162), 4 phase 11 trials (n = 171), and 1 phase Ib trial (sample size unknown), while no randomized controlled trial was found. Ipilimumab monotherapy was assessed at 3 mg/kg in 5 trials (n = 186) with a response rate of 0 to 5%. Two reports investigated ipilimumab at 10 mg/kg (n = 45) with radiological responses observed in 0 to 6.5%. The median progression-free survival (PFS) was below 3 months and the median overall survival was 5.2-9.8 months for ipilimumab monotherapy. Severe immune-related adverse events occurred at a frequency comparable to cutaneous melanoma (6 to 36%). Two studies investigated pembrolizumab (2 mg/kg) and nivolumab (3 mg/kg) with overall response rates of 30% and 6%, respectively. Data on combined ipilimumab and programmed cell death protein 1 inhibition were available from one expanded access program, but no response was observed with a median PFS of 2.9 months. Conclusions: UM is little responsive to ipilimumab regardless of dosage schemes. Sound randomized clinical trials are needed to evaluate the efficacy of combined ICB in patients with UM.

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