title: Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT).
abstract: Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS.
  
  
  
  An open-label prospective phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma.
  
  
  
  Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS+). The 1-year OS rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response (GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile.
  
  
  
  Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study.This study is registered at www.clinicatrials.gov NCT00942162.
authors: General Dermatology and Oncology Service, Ambroise-Paré Hospital, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne, France philippe.saiag@uvsq.fr.
authors: P
authors: P
authors: Saiag
authors: Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany.
authors: R
authors: R
authors: Gutzmer
authors: National Institute for Tumors Foundation 'G. Pascale', Napoli.
authors: P A
authors: PA
authors: Ascierto
authors: Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
authors: M
authors: M
authors: Maio
authors: Department of Dermatology and Skin Cancers, La Timone APHM Hospital, Aix-Marseille University, Marseille, France.
authors: J-J
authors: JJ
authors: Grob
authors: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland.
authors: P
authors: P
authors: Murawa
authors: Dermatology Clinic, Hôtel-Dieu Hospital, CHU Nantes, Nantes, France.
authors: B
authors: B
authors: Dreno
authors: Department of Surgical Oncology, UTMD Anderson Cancer Center, Houston.
authors: M
authors: M
authors: Ross
authors: Moffitt Cancer Center, Tampa, USA.
authors: J
authors: J
authors: Weber
authors: Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors: A
authors: A
authors: Hauschild
authors: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Center and Institute of Oncology, Warsaw, Poland.
authors: P
authors: P
authors: Rutkowski
authors: Melanoma and Soft Tissue Sarcoma Division, European Institute of Oncology, Milan, Italy.
authors: A
authors: A
authors: Testori
authors: Petrov Research Institute of Oncology, St Petersburg, Russian Federation.
authors: E
authors: E
authors: Levchenko
authors: Department of Dermatology, University of Heidelberg, Heidelberg, Germany.
authors: A
authors: A
authors: Enk
authors: Department of Dermatology, University Hospital of Brest, Brest, France.
authors: L
authors: L
authors: Misery
authors: GSK Vaccines, Rixensart, Belgium.
authors: C
authors: C
authors: Vanden Abeele
authors: GSK Vaccines, Rixensart, Belgium.
authors: I
authors: I
authors: Vojtek
authors: GSK Vaccines, Rixensart, Belgium.
authors: O
authors: O
authors: Peeters
authors: GSK Vaccines, Rixensart, Belgium.
authors: V G
authors: VG
authors: Brichard
authors: GSK Vaccines, Rixensart, Belgium.
authors: P
authors: P
authors: Therasse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D009367:Neoplasm Staging; D059467:Transcriptome / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins
keywords: MAGE-A3 antigen; gene signature; immunotherapy; melanoma; predictive biomarkers