PMID- 27043866
OWN - NLM
STAT- MEDLINE
DCOM- 20170703
LR  - 20220409
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Print)
IS  - 0959-8049 (Linking)
VI  - 60
DP  - 2016 Jun
TI  - Characterisation and management of dermatologic adverse events to agents 
      targeting the PD-1 receptor.
PG  - 12-25
LID - S0959-8049(16)00125-8 [pii]
LID - 10.1016/j.ejca.2016.02.010 [doi]
AB  - BACKGROUND: Dermatologic adverse events (AEs) are some of the most frequently 
      observed toxicities of immune-checkpoint inhibitor therapy, but they have 
      received little attention. The drugs, pembrolizumab and nivolumab are recently 
      approved inhibitors of the programmed death (PD)-1 receptor that have overlapping 
      AE profiles however, the incidence, relative risk (RR), and clinico-morphological 
      pattern of the associated dermatologic AEs are not known. METHODS: We conducted a 
      systematic review of the literature, and performed a meta-analysis of 
      dermatologic AEs observed with the use of pembrolizumab and nivolumab in cancer 
      patients. An electronic search was conducted using the PubMed, and Web of 
      Science, and on the American Society of Clinical Oncology and European Society 
      for Medical Oncology meeting abstracts' libraries for potentially relevant 
      oncology trials, that employed the drugs at Food and Drug Administration-approved 
      doses and reported dermatologic AEs. The incidence, RR and 95% confidence 
      intervals were calculated using either random- or fixed-effects models based on 
      the heterogeneity of included studies. The clinical presentation, histology of 
      affected skin areas, and management strategies (based on institutional 
      experience), are also presented. RESULTS: Rash, pruritus and vitiligo were found 
      to be the most frequently reported dermatologic AEs. The calculated incidence of 
      all-grade rash with pembrolizumab and nivolumab was 16.7% (RR = 2.6) and 14.3% 
      (RR = 2.5), respectively. Other significant all-grade AEs included pruritus 
      (pembrolizumab: incidence, 20.2% [RR = 49.9]; nivolumab: incidence, 13.2% 
      [RR = 34.5]) and vitiligo (pembrolizumab: incidence, 8.3% [RR = 17.5]; nivolumab: 
      7.5% [RR = 14.6]). Interestingly, all the vitiligo events were reported in trials 
      investigating melanoma. The RR for developing dermatologic AEs in general, was 
      2.95 with pembrolizumab, and 2.3 with nivolumab. CONCLUSION: We found that 
      pembrolizumab and nivolumab are both associated with dermatologic AEs, primarily 
      low-grade rash, pruritus, and vitiligo, which are reminiscent of those seen with 
      ipilimumab. Knowledge of these findings is critical for optimal care, maintaining 
      dose intensity, and health-related quality of life in cancer patients receiving 
      PD-1 inhibitors.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Belum, V R
AU  - Belum VR
AD  - Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
FAU - Benhuri, B
AU  - Benhuri B
AD  - Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 
      College of Medicine and Life Sciences, University of Toledo, Health Science 
      Campus, 3000 Arlington Avenue, Toledo, OH, USA.
FAU - Postow, M A
AU  - Postow MA
AD  - Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, 
      New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
FAU - Hellmann, M D
AU  - Hellmann MD
AD  - Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA; Weill Cornell Medical College, New York, NY, USA.
FAU - Lesokhin, A M
AU  - Lesokhin AM
AD  - Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill 
      Cornell Medical College, New York, NY, USA.
FAU - Segal, N H
AU  - Segal NH
AD  - Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New 
      York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
FAU - Motzer, R J
AU  - Motzer RJ
AD  - Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, 
      NY, USA; Weill Cornell Medical College, New York, NY, USA.
FAU - Wu, S
AU  - Wu S
AD  - Division of Medical Oncology, Department of Medicine, State University of New 
      York at Stony Brook, Stony Brook, NY, USA; Division of Hematology and Oncology, 
      Department of Medicine, Northport VA Medical Center, Northport, NY, USA.
FAU - Busam, K J
AU  - Busam KJ
AD  - Pathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 
      Weill Cornell Medical College, New York, NY, USA.
FAU - Wolchok, J D
AU  - Wolchok JD
AD  - Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, 
      New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
FAU - Lacouture, M E
AU  - Lacouture ME
AD  - Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 
      Weill Cornell Medical College, New York, NY, USA. Electronic address: 
      lacoutum@mskcc.org.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20160401
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 31YO63LBSN (Nivolumab)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/*adverse effects
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Antineoplastic Agents/*adverse effects
MH  - Cell Cycle Checkpoints/drug effects
MH  - Clinical Trials as Topic
MH  - Drug Eruptions/*etiology
MH  - Exanthema/chemically induced
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Nivolumab
MH  - Programmed Cell Death 1 Receptor/antagonists & inhibitors
MH  - Pruritus/chemically induced
MH  - Vitiligo/chemically induced
MH  - Young Adult
PMC - PMC4998047
MID - NIHMS809930
OTO - NOTNLM
OT  - Adverse events
OT  - Immune-checkpoint
OT  - Immunotherapy
OT  - Nivolumab
OT  - PD-1
OT  - Pembrolizumab
OT  - Programmed death-1
OT  - Pruritus
OT  - Rash
OT  - Vitiligo
COIS- STATEMENT VRB, BB, MDH, NHS, RJM, and KJB have no conflicts of interest to 
      declare. MAP has had a consulting or advisory role with Amgen and Bristol-Myers 
      Squibb, and receives research support from Bristol-Myers Squibb and Novartis 
      (Inst). AML has a consulting or advisory role with Bristol-Myers Squibb, Janssen, 
      Aduro, Efranat, Jounce, and Novartis, and receives research funding from 
      Bristol-Myers Squibb (Inst), Janssen (Inst.), and Genentech (Inst). SW has a 
      speaking arrangement with Novartis, Bayer-Onyx, Pfizer, and Mediavation. JDW has 
      a consulting or advisory role with Bristol-Myers Squibb, Merck, MedImmune, 
      Ziopharm, Polynoma, Polaris, Jounce, GlaxoSmithKline; receives honoraria from EMD 
      Serono, Janssen Oncology, and research funding from Bristol-Myers Squibb (Inst), 
      MedImmune (Inst), GlaxoSmithKline (Inst), Merck (Inst). MEL has consulted for BMS 
      and Merck, and received research support from Bristol-Myers Squibb (Inst).
EDAT- 2016/04/05 06:00
MHDA- 2017/07/04 06:00
PMCR- 2017/06/01
CRDT- 2016/04/05 06:00
PHST- 2015/12/23 00:00 [received]
PHST- 2016/02/12 00:00 [accepted]
PHST- 2016/04/05 06:00 [entrez]
PHST- 2016/04/05 06:00 [pubmed]
PHST- 2017/07/04 06:00 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - S0959-8049(16)00125-8 [pii]
AID - 10.1016/j.ejca.2016.02.010 [doi]
PST - ppublish
SO  - Eur J Cancer. 2016 Jun;60:12-25. doi: 10.1016/j.ejca.2016.02.010. Epub 2016 Apr 
      1.