PMID- 27467964
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160729
LR  - 20240210
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 5
IP  - 5
DP  - 2016 May
TI  - Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients 
      with uveal melanoma.
PG  - e1143997
LID - 10.1080/2162402X.2016.1143997 [doi]
LID - e1143997
AB  - BACKGROUND: 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. 
      METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
FAU - Karydis, Ioannis
AU  - Karydis I
AD  - Cancer Sciences Academic Unit, University of Southampton , Southampton, United 
      Kingdom.
FAU - Chan, Pui Ying
AU  - Chan PY
AD  - Department of Medical Oncology, St Bartholomew's Hospital , London.
FAU - Wheater, Matthew
AU  - Wheater M
AD  - Medical Oncology, University Hospital Southampton , Southampton, United Kingdom.
FAU - Arriola, Edurne
AU  - Arriola E
AD  - Medical Oncology, University Hospital Southampton , Southampton, United Kingdom.
FAU - Szlosarek, Peter W
AU  - Szlosarek PW
AD  - Department of Medical Oncology, St Bartholomew's Hospital, London; Barts Cancer 
      Institute, Queen Mary University of London, London.
FAU - Ottensmeier, Christian H
AU  - Ottensmeier CH
AD  - Cancer Sciences Academic Unit, University of Southampton , Southampton, United 
      Kingdom.
LA  - eng
GR  - 18892/CRUK_/Cancer Research UK/United Kingdom
GR  - 15951/CRUK_/Cancer Research UK/United Kingdom
GR  - 22795/CRUK_/Cancer Research UK/United Kingdom
GR  - 18158/CRUK_/Cancer Research UK/United Kingdom
GR  - 12135/CRUK_/Cancer Research UK/United Kingdom
GR  - 18161/CRUK_/Cancer Research UK/United Kingdom
GR  - 20613/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160218
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
PMC - PMC4910726
OTO - NOTNLM
OT  - Anti-PD-1
OT  - Pembrolizumab
OT  - immuno-oncology
OT  - metastases
OT  - uveal melanoma
EDAT- 2016/07/29 06:00
MHDA- 2016/07/29 06:01
PMCR- 2016/02/18
CRDT- 2016/07/29 06:00
PHST- 2015/10/02 00:00 [received]
PHST- 2016/01/12 00:00 [revised]
PHST- 2016/01/14 00:00 [accepted]
PHST- 2016/07/29 06:00 [entrez]
PHST- 2016/07/29 06:00 [pubmed]
PHST- 2016/07/29 06:01 [medline]
PHST- 2016/02/18 00:00 [pmc-release]
AID - 1143997 [pii]
AID - 10.1080/2162402X.2016.1143997 [doi]
PST - epublish
SO  - Oncoimmunology. 2016 Feb 18;5(5):e1143997. doi: 10.1080/2162402X.2016.1143997. 
      eCollection 2016 May.