Complete Title: GU Cancers Symposium 2013 - Aflibercept versus placebo in combination with docetaxel/prednisone for first-line treatment of men with metastatic castration-resistant prostate cancer (mCRPC): Results from the multinational phase III trial (VENICE), by Ian F. Tannock , MD, FRCPC, PhD, et al. - Session Highlights
ORLANDO, FL, USA (UroToday.com) - Docetaxel/prednisone is standard first-line chemotherapy for mCRPC. Aflibercept is an anti-angiogenic agent that inhibits angiogenesis by binding VEGF-A, VEGF-B and placental growth factor (PlGF). VENICE is a double-blind, randomized phase III study with overall survival (OS) as primary endpoint in men with mCRPC without prior cytotoxic treatment. Secondary endpoints were PSA response, time to skeletal-related events (SRE), and progression-free survival (PFS). They were treated with docetaxel (75 mg/m2 iv q3w) and oral prednisone (5 mg bid) and were randomized to receive either Aflibercept (A) 6 mg/kg or placebo (P) IV every 3 weeks. Between August 2007 and February 2010, 1 224 patients were randomized (n=612 in both arms) and for final OS analysis, 873 deaths were required. Baseline characteristics were very similar between the groups, and median age was 68 years. The median number of treatment cycles were 8 (A) and 9 (P). At final cut-off, when 873 patients had died; median follow up was 35.4 month. At this point the results were as follow: Median-OS 22.1 months (A) vs. 21.2 months (P) (HR=0.94, 0.82-1.08, p=0.38), PSA response 68.6% (A) vs. 63.5% (P) (p= 0.075), Time to SRE 15.3 months (A) vs. 15.0 months (P) (HR=0.94, 0.83-1.06, p= 0.31), and PFS 6.9 months (A) vs. 6.2 months (P) (p=0.31). Median treatment time was 24 months (A) and 28.9 months (P).
Higher incidence of all-grade adverse events (AE) was observed in the A-arm, and discontinuation due to AEs was higher in the A-arm. Fatal AEs were seen at a higher rate in the A-arm, 5.6% vs. 3.3% in the P-arm.
To conclude, aflibercept in combination with docetaxel/prednisone as first line chemotherapy did not show a statistically significant improvement in OS in men with mCRPC, and the secondary endpoints were all very similar between the two arms. In addition, toxicity was higher in the aflibercept-arm. In summary, this was another negative trial where a targeted agent has been added to docetaxel/prednisone as first line chemotherapy in men with mCRPC.
Presented by Ian Tannock, Karim Fizazi, Sergei Ivanov, Camilla Thellenberg Karlsson, Aude Flechon, Iwona Anna Skoneczna, Francisco Jorquera Orlandi, Gwenaelle Gravis, Vsevolod B. Matveev, Sevil E. Bavbek, Thierry Gil, Luciano S. Viana, Osvaldo Rudy Aren, Oleg Karyakin, Tony Elliott, Alison J. Birtle, Emmanuelle Magherini, Laurence Hatteville, Bertrand Tombal, Mark Rosenthal, and The VENICE Investigators at the 2013 Genitourinary Cancers Symposium - February 14 - 16, 2013 - Rosen Shingle Creek - Orlando, Florida USA
Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada; Institut Gustave Roussy, Villejuif, France; Russian Science Center of X-ray, Moscow, Russia; Onkologiska kliniken Norrlands Universitetssjukhus,, Umea, Sweden; Centre Léon Bérard, Lyon, France; Institute of Oncology, Warsaw, Poland; OncoMed Pharmaceuticals, Providencia, Chile; Department of Medical Oncology, Institut Paoli Calmettes, Marseille, France; N.N. Blokhin Cancer Research Center, Moscow, Russia; Istanbul University Oncology Institute, Istanbul, Turkey; Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Barretos Cancer Hospital, Barretos, Brazil; Instituto Nacional del Cancer Oncology, Santiago, Chile; Medical Radiological Research Center, Obninsk, Russia; Christie NHS Foundation Trust, Manchester, United Kingdom; Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom; Research and Development, Sanofi, Vitry sur Seine, France; Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Royal Melbourne Hospital, Parkville, Australia
Written by Anna Forsberg, medical reporter for UroToday.com
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