title: The efficacy of anti-PD-1 agents in acral and mucosal melanoma.
abstract: BACKGROUND
  Therapeutic antibodies against programmed cell death receptor 1 (PD-1) are considered front-line therapy in metastatic melanoma. The efficacy of PD-1 blockade for patients with biologically distinct melanomas arising from acral and mucosal surfaces has not been well described.
  
  
  METHODS
  A multi-institutional, retrospective cohort analysis identified adults with advanced acral and mucosal melanoma who received treatment with nivolumab or pembrolizumab as standard clinical practice through expanded access programs or published prospective trials. Objective responses were determined using investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival and overall survival were assessed using the Kaplan-Meier method.
  
  
  RESULTS
  Sixty individuals were identified, including 25 (42%) with acral melanoma and 35 (58%) with mucosal melanoma. Fifty-one patients (85%) had received previous therapy, including 77% who had previously received ipilimumab. Forty patients (67%) received pembrolizumab at a dose of 2 mg/kg or 10 mg/kg, and 20 (33%) received nivolumab at a doses ranging from 0.3 to 10 mg/kg every 2 to 3 weeks. The objective response rate was 32% (95% confidence interval, 15%-54%) in patients with acral melanoma and 23% (95% confidence interval, 10%-40%) in those with mucosal melanoma. After a median follow-up of 20 months in the acral melanoma group and 10.6 months in the mucosal melanoma group, the median progression-free survival was 4.1 months and 3.9 months, respectively. Only 2 patients (3%) discontinued treatment because of toxicity.
  
  
  CONCLUSIONS
  Response rates to PD-1 blockade in patients with acral and mucosal melanomas were comparable to the published rates in patients with cutaneous melanoma and support the routine use of PD-1 blockade in clinical practice. Further investigation is needed to identify the mechanisms of response and resistance to therapy in these subtypes. Cancer 2016;122:3354-3362. © 2016 American Cancer Society.
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York. shoushta@mskcc.org.|Weill Cornell Medical College, New York, New York. shoushta@mskcc.org.
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: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kuk
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: Katy K
authors.initials: KK
authors.lastname: Tsai
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Washington, District of Columbia.
authors.forename: Suthee
authors.initials: S
authors.lastname: Rapisuwon
authors.affiliation: Moffitt Cancer Center, Tampa, Florida.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Eroglu
authors.affiliation: Massachussetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
authors.affiliation: University of Chicago Comprehensive Cancer Center Chicago, Illinois.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Luke
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Tara C
authors.initials: TC
authors.lastname: Gangadhar
authors.affiliation: Duke University School of Medicine, Durham, North Carolina.
authors.forename: April K S
authors.initials: AK
authors.lastname: Salama
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Varina
authors.initials: V
authors.lastname: Clark
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Clare
authors.initials: C
authors.lastname: Burias
authors.affiliation: Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee.
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Washington, District of Columbia.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Alain P
authors.initials: AP
authors.lastname: Algazi
authors.affiliation: Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York.|Weill Cornell Medical College, New York, New York.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York.|Weill Cornell Medical College, New York, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
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*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary*; 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 / Q000037:antagonists & inhibitors* / Q000276:immunology; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: acral melanoma; anti-programmed cell death receptor 1 (anti-PD-1); immunotherapy; mucosal melanoma; nivolumab; pembrolizumab