title: Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies.
abstract: BACKGROUND
  Antibodies inhibiting the programmed death receptor 1 (PD-1) have demonstrated significant activity in the treatment of advanced cutaneous melanoma. The efficacy and safety of PD-1 blockade in patients with uveal melanoma has not been well characterized.
  
  
  METHODS
  Fifty-eight patients with stage IV uveal melanoma received PD-1 or PD-1 ligand (PD-L1) antibodies between 2009 and 2015 at 9 academic centers. Patients who were evaluable for response were eligible for the analysis. Imaging was performed every 12 weeks and at the investigators' discretion. Safety and clinical efficacy outcomes, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively determined.
  
  
  RESULTS
  Of 56 eligible patients, 48 (86%) had received prior therapy, and 35 (63%) had received treatment with ipilimumab. Three patients had an objective response to ipilimumab, and 8 had stable disease as their best response. Thirty-eight patients (68%) received pembrolizumab, 16 (29%) received nivolumab, and 2 (4%) received atezolizumab. Objective tumor responses were observed in 2 patients for an overall response rate of 3.6% (95% confidence interval [CI], 1.8%-22.5%). Stable disease (≥6 months) was observed in 5 patients (9%). The median PFS was 2.6 months (95% CI, 2.4-2.8 months), and the median OS was 7.6 months (95% CI, 0.7-14.6 months). There was no association between prior treatment with ipilimumab or liver-directed therapy and PFS or OS. Treatment was well tolerated, and only 1 patient discontinued treatment because of toxicity.
  
  
  CONCLUSIONS
  PD-1 and PD-L1 antibodies rarely confer durable remissions in patients with metastatic uveal melanoma. Clinical trial enrollment should be prioritized in this population. Cancer 2016;122:3344-3353. © 2016 American Cancer Society.
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California. alain.algazi@ucsf.edu.
authors.forename: Alain P
authors.initials: AP
authors.lastname: Algazi
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Katy K
authors.initials: KK
authors.lastname: Tsai
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Shoushtari
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Rodrigo R
authors.initials: RR
authors.lastname: Munhoz
authors.affiliation: Moffitt Cancer Center, Tampa, Florida.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Eroglu
authors.affiliation: Spanish Melanoma Multidisciplinary Group, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Piulats
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Ott
authors.affiliation: Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Johnson
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Adil I
authors.initials: AI
authors.lastname: Daud
authors.affiliation: Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.affiliation: Columbia University Medical Center, New York, New York.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
authors.affiliation: Johansson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
authors.affiliation: Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, New York.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology*; D009367:Neoplasm Staging; D000077594:Nivolumab; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D012189:Retrospective Studies; D012878:Skin Neoplasms; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma; D000098943:Uveal Melanoma
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: atezolizumab; immunotherapy; nivolumab; pembrolizumab; uveal melanoma