Randomized, Placebo-Controlled, Phase III Trial of Sunitinib Plus Prednisone Versus Prednisone Alone in Progressive, Metastatic, Castration-Resistant Prostate Cancer

TY - JOUR

T1 - Randomized, Placebo-Controlled, Phase III Trial of Sunitinib Plus Prednisone Versus Prednisone Alone in Progressive, Metastatic, Castration-Resistant Prostate Cancer

AU - Michaelson, M Dror

AU - Oudard, Stephane

AU - Ou, Yen-Chuan

AU - Sengeløv, Lisa

AU - Saad, Fred

AU - Houede, Nadine

AU - Ostler, Peter

AU - Stenzl, Arnulf

AU - Daugaard, Gedske

AU - Jones, Robert

AU - Laestadius, Fredrik

AU - Ullèn, Anders

AU - Bahl, Amit

AU - Castellano, Daniel

AU - Gschwend, Juergen

AU - Maurina, Tristan

AU - Chow Maneval, Edna

AU - Wang, Shaw-Ling

AU - Lechuga, Maria Jose

AU - Paolini, Jolanda

AU - Chen, Isan

PY - 2014/1/10

Y1 - 2014/1/10

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Anemia

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Asthenia

KW - Disease Progression

KW - Disease-Free Survival

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Drug Resistance, Neoplasm

KW - Fatigue

KW - Humans

KW - Indoles

KW - Kaplan-Meier Estimate

KW - Lymphopenia

KW - Male

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Orchiectomy

KW - Prednisone

KW - Prostatic Neoplasms

KW - Pyrroles

KW - Taxoids

KW - Treatment Outcome

U2 - 10.1200/jco.2012.48.5268

DO - 10.1200/jco.2012.48.5268

M3 - Journal article

C2 - 24323035

SN - 0732-183X

VL - 32

SP - 76

EP - 82

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 2

ER -