1General Dermatology and Oncology Service, Ambroise-Paré Hospital, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne, France2Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany3National Institute for Tumors Foundation ‘G. Pascale’, Napoli4Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy5Department of Dermatology and Skin Cancers, La Timone APHM Hospital, Aix-Marseille University, Marseille, France6Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland7Dermatology Clinic, Hôtel-Dieu Hospital, CHU Nantes, Nantes, France8Department of Surgical Oncology, UTMD Anderson Cancer Center, Houston9Moffitt Cancer Center, Tampa, USA10Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany11Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Center and Institute of Oncology, Warsaw, Poland12Melanoma and Soft Tissue Sarcoma Division, European Institute of Oncology, Milan, Italy13Petrov Research Institute of Oncology, St Petersburg, Russian Federation14Department of Dermatology, University of Heidelberg, Heidelberg, Germany15Department of Dermatology, University Hospital of Brest, Brest, France16GSK Vaccines, Rixensart, Belgium
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BackgroundGenomic 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.Patients and methodsAn open-label prospective phase II trial (‘PREDICT’) in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma.ResultsOf 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.ConclusionTreatment 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.