title: Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program.
abstract: BACKGROUND
  The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program.
  
  
  METHODS
  Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group.
  
  
  RESULTS
  Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events.
  
  
  CONCLUSIONS
  Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.
authors.affiliation: Translational Cancer Research Unit, Dr. Rosell Oncology Institute, Quiron Dexeus University Hospital, 08028, Barcelona, Spain. mgonzalezcao@oncorosell.com.
authors.forename: M
authors.initials: M
authors.lastname: González-Cao
authors.affiliation: Hospital Clinic I Provincial, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Arance
authors.affiliation: Catalan Institute of Oncology, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Piulats
authors.affiliation: Gregorio Marañón Institute of Health Research, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Marquez-Rodas
authors.affiliation: Germans Trias I Pujol University Hospital, Barcelona, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Manzano
authors.affiliation: General University Hospital, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Berrocal
authors.affiliation: Burgos University Hospital, Burgos, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Crespo
authors.affiliation: Insular University Hospital of Gran Canaria, Canary Islands, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Rodriguez
authors.affiliation: Costa del Sol Hospital, Marbella, Malaga, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Perez-Ruiz
authors.affiliation: Regional University Hospital of Malaga, Malaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Berciano
authors.affiliation: Ramony Cajal Hospital, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Soria
authors.affiliation: Marqués de Valdecilla University Hospital, Santander, Spain.
authors.forename: A G
authors.initials: AG
authors.lastname: Castano
authors.affiliation: La Paz University Hospital, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Espinosa
authors.affiliation: Del Mar University Hospital, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Montagut
authors.affiliation: Virgen de la Victoria Hospital, Malaga, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Alonso
authors.affiliation: Miguel Servet University Hospital, Zaragoza, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Puertolas
authors.affiliation: San Carlos Hospital, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Aguado
authors.affiliation: Dr. Peset Hospital, Valencia, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Royo
authors.affiliation: Consorci Sanitari de Terrassa, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Clara Campal Hospital, Madrid, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: Rodríguez
authors.affiliation: Valld'Hebron University Hospital, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Muñoz
authors.affiliation: Son Llatzer University Hospital, Mallorca, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Mut
authors.affiliation: National Cancer Institute, Mexico City, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Barron
authors.affiliation: Navarra University Clinic, Pamplona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Martin-Algarra
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D013030:Spain; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C582435:pembrolizumab
keywords: CNS metastases; Expanded access program; Melanoma; Pembrolizumab; Survival