title: Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma.
abstract: Untreated metastatic uveal melanoma (UM) carries a grave prognosis. Unlike cutaneous melanoma (CM), there are no established treatments known to significantly improve outcomes for a meaningful proportion of patients. Inhibition of the PD1-PDL1 axis has shown promise in the management of CM and we here report a two center experience of UM patients receiving pembrolizumab.
  
  
  
  To assess the efficacy and safety of pembrolizumab, we retrospectively analyzed outcome data of 25 consecutive UM patients participating in the MK3475 expanded access program (EAP) who received pembrolizumab at 2 mg/kg 3 weekly. Tumor assessment was evaluated using RECIST 1.1 and immune-related Response Criteria (irRC) by CT scanning. Toxicity was recorded utilizing Common Terminology Criteria for Adverse Events ("CTCAE") v4.03.
  
  
  
  Twenty-five patients were identified receiving a median of six cycles of treatment. Two patients achieved a partial response and six patients stable disease. After a median follow-up of 225 d median progression free survival (PFS) was 91 d and overall survival (OS) was not reached. There was a significant trend for improved outcomes in patients with extrahepatic disease progression as opposed to liver only progression at the outset. Five patients experienced grade 3 or 4 adverse events (AEs); there were no treatment related deaths.
  
  
  
  Pembrolizumab 2mg/kg q3w is a safe option in UM patients. Disease control rates, particularly in the subgroup of patients without progressive liver disease at the outset are promising; these results merit further investigation in clinical trials possibly incorporating liver targeted treatment modalities.
authors.affiliation: Cancer Sciences Academic Unit, University of Southampton , Southampton, United Kingdom.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Karydis
authors.affiliation: Department of Medical Oncology, St Bartholomew's Hospital , London.
authors.forename: Pui Ying
authors.initials: PY
authors.lastname: Chan
authors.affiliation: Medical Oncology, University Hospital Southampton , Southampton, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wheater
authors.affiliation: Medical Oncology, University Hospital Southampton , Southampton, United Kingdom.
authors.forename: Edurne
authors.initials: E
authors.lastname: Arriola
authors.affiliation: Department of Medical Oncology, St Bartholomew's Hospital, London; Barts Cancer Institute, Queen Mary University of London, London.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Szlosarek
authors.affiliation: Cancer Sciences Academic Unit, University of Southampton , Southampton, United Kingdom.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Ottensmeier
keywords: Anti-PD-1; Pembrolizumab; immuno-oncology; metastases; uveal melanoma