Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma and methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter: Key results of the multicenter, randomized, open-label, controlled, phase III CENTRIC study.

Central Nervous System Tumors
Session Type and Session Title: 
Clinical Science Symposium, Predictive Molecular Biomarkers: Enriching Clinical Trial Populations for Gliomas
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr LBA2009)
Roger Stupp, Monika E. Hegi, Thierry Gorlia, Sara Erridge, Danica Grujicic, Joachim Peter Steinbach, Wolfgang Wick, Rafal Tarnawski, Do-Hyun Nam, Astrid Weyerbrock, Peter Hau, Martin JB Taphoorn, Louis B. Nabors, David A. Reardon, Martin J. Van Den Bent, James R. Perry, Yong Kil Hong, Christine Hicking, Martin Picard, Michael Weller, on behalf of the European Organisation for Research and Treatment of Cancer (EORTC), the Canadian Brain Tumor Consortium, and the CENTRIC Study Team; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; EORTC Data Centre, Brussels, Belgium; Edinburgh Cancer Research UK Centre, Edinburgh, United Kingdom; Institute for Neurosurgery, Clinical Center Serbia, Belgrade, Serbia; Klinikum der J.W. Goethe Universität Frankfurt, Dr. Senkenbergisches Institut für Neuroonkologie, Frankfurt, Germany; Universitätsklinikum Heidelberg, Heidelberg, Germany; Maria Sklodowska-Curie Memorial Cancer-Center and Institute of Oncology Gliwice Branch, Radiotherapy and Chemotherapy Clinic, Gliwice, Poland; Samsung Medical Center, Seoul, South Korea; Universitätsklinikum Freiburg, Allgemeine Neurochirurgie, Freiburg, Germany; Universitätsklinikum Regensburg, Neurologie und Wilhelm Sander-Therapieeinheit NeuroOnkologie, Regensburg, Germany; Medical Center Haaglanden, The Hague, Netherlands; University of Alabama at Birmingham, Birmingham, AL; Dana-Farber Cancer Institute, Boston, MA; Erasmus MC, Rotterdam, Netherlands; Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Catholic University of Korea, Seoul St Marys Hospital, Seoul, South Korea; Merck KGaA, Darmstadt, Germany; University Hospital Zurich, Zurich, Switzerland

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Abstract Disclosures


Background: Cilengitide (CIL) is a selective αvβ3 and αvβ5 integrin inhibitor. In a phase II study in patients with newly diagnosed glioblastoma, CIL added to standard temozolomide (TMZ) and radiotherapy (RT) was well tolerated and appeared to confer improved survival in patients with glioblastoma and methylated MGMT gene promoter (Stupp et al. J Clin Oncol. 2010;28:2712-8). Methods: This multicenter, randomized, controlled, open-label, phase III study randomized (1:1) patients (≥ 18 years) with newly diagnosed, histologically proven supratentorial glioblastoma (WHO Grade IV) and centrally determined MGMT gene promoter methylation. Treatment consisted of CIL 2000 mg twice weekly i.v. plus standard TMZ/RT→TMZ (concomitant and adjuvant temozolomide and radiotherapy; Stupp et al. N Engl J Med. 2005;352:987-96) or standard TMZ/RT→TMZ alone. CIL was to be administered for ≥ 18 months, or until disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) per investigator read and safety. Results: 272 patients received CIL plus TMZ/RT→TMZ, and 273 were treated with TMZ/RT→TMZ alone (intention-to-treat population). 54% and 52% of patients were male, and 42% and 44% had ECOG-PS ≥ 1, respectively. 75% of patients of both arms were ≥ 50 years old. Overall, baseline characteristics were well balanced across treatment arms. Median OS was 26.3 months in both arms (Hazard Ratio [HR] = 1.02 [95%CI: 0.81-1.29], p = 0.86). Median PFS per investigator read was 13.5 months in the CIL arm and 10.7 months in the control arm (HR = 0.93 [95%CI: 0.76-1.14], p = 0.48). Treatment was generally well tolerated and the known safety profile of CIL was confirmed. Conclusions: CIL failed to prolong PFS or OS in patients with newly diagnosed glioblastoma and methylated MGMT gene promoter. The previously reported safety profile of CIL in addition to standard therapy was confirmed. Clinical trial information: NCT00689221.