PURPOSE: We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC).
PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned.
RESULTS: Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%).
CONCLUSION: The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.
Written by:
Michaelson MD, Oudard S, Ou YC, Sengeløv L, Saad F, Houede N, Ostler P, Stenzl A, Daugaard G, Jones R, Laestadius F, Ullèn A, Bahl A, Castellano D, Gschwend J, Maurina T, Chow Maneval E, Wang SL, Lechuga MJ, Paolini J, Chen I. Are you the author?
Massachusetts General Hospital Cancer Center, Boston, MA; George Pompidou European Hospital, Rene Descartes University, Paris; Institut Bergonie, Bordeaux; CHU de Besançon, Hôpital Jean Minjoz, Besançcon, France; Taichung Veterans General Hospital, Taichung, Taiwan; Herlev Hospital, Herlev; Rigshospitalet, Copenhagen, Denmark; University of Montreal, Montreal, Canada; Mount Vernon Hospital, Northwood, Middlesex; Beatson West of Scotland Cancer Centre, Glasgow; Bristol Haematology and Oncology Centre, Bristol, UK; Eberhard-Karls-University Medical School, Tübingen; Technical University of Munich, Munich, Germany; Karolinska University Hospital, Stockholm, Sweden; I_12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain; Pfizer Oncology, La Jolla, CA; Pfizer Oncology, Milan, Italy.
Reference: J Clin Oncol. 2013 Dec 9. Epub ahead of print.
doi: 10.1200/JCO.2012.48.5268
PubMed Abstract
PMID: 24323035
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