937P - Denosumab in patients with metastatic prostate cancer previously treated with denosumab or zoledronic acid: 2-year open-label extension phase result...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Supportive Measures
Prostate Cancer
Presenter Karim Fizazi
Authors J. Brown1, M. Carducci2, N.D. Shore3, P. Sieber4, F. Kueppers5, L.I. Karsh6, R. Wei7, C. Goessl8
  • 1Medical Oncology, Cancer Research UK Clinical Centre, Universities of Leeds/Sheffield, Leeds/UK
  • 2Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore/US
  • 3Urology, Carolina Urologic Research Center, Myrtle Beach/US
  • 4Urology And Urological Surgery, Urological Associates of Lancaster, Ltd., Lancaster/US
  • 5Urology, Urology Associates, Christchurch/NZ
  • 6Clinical Research Department, The Urology Center of Colorado, Denver/US
  • 7Global Biostatistical Science, Amgen Inc., Thousand Oaks/US
  • 8Clinical Development, Amgen Inc., Thousand Oaks/US



In a phase 3, randomized, double-blinded (DB) trial (NCT00321620), subcutaneous (SC) denosumab prevented skeletal-related events (SRE) more effectively compared with intravenous (IV) zoledronic acid (ZA) in men with castration-resistant prostate cancer (CRPC) and bone metastases (Fizazi K et al., Lancet 2011). As a result, all patients (pts) remaining on study were offered open-label (OL) denosumab in a pre-specified 2-year extension phase.

Materials and methods

Pts (n = 1901) with CRPC metastatic to bone received either SC denosumab 120 mg and IV placebo or IV ZA 4 mg (adjusted for renal function) and SC placebo Q4W in the DB treatment phase. OL denosumab Q4W was offered for up to 2 years to pts remaining on study. Pts declining OL treatment were followed for survival for up to 2 years after their last dose of investigational product in the DB treatment phase.


Of 323 pts completing the DB phase, 153 (87.4%) who were randomized to denosumab (here referred to as DD pts) and 128 (86.5%) randomized to ZA (here referred to as ZD pts) continued in the OL phase. Demographics were balanced between groups. Cumulative median (Q1, Q3) denosumab exposure over the entire study for DD pts was 12.0 (5.6, 21.3) months (range: 0.1 to 67.2 months). Overall, adverse events (AEs) were comparable between groups (n = 138/147 [93.9%] DD pts; n = 105/118 [89.0%] ZD pts). Twelve pts in the DD group and 7 pts in the ZD group developed osteonecrosis of the jaw (ONJ) in the OL phase, resulting in a cumulative ONJ incidence for the entire study of 3.8% for DD pts and 2.2% for ZD pts. Hypocalcemia AEs during the OL phase were balanced between groups (n = 8 DD pts; n = 5 ZD pts). Serious AEs were reported in 78 (53.1%) DD pts and 63 (53.4%) ZD pts. Median (95% CI) overall survival over the entire study was similar between groups: 19.4 months (17.8 to 21.0) for DD pts, 19.3 months (18.0 to 20.6) for ZD pts.


This two-year OL extension treatment phase confirmed the long-term safety profile of denosumab in pts with prostate cancer metastatic to bone who received denosumab for up to 5.6 years or who switched from ZA to denosumab.


K. Fizazi: Consultant/advisor: Amgen, Novartis,

J.E. Brown: Advisory Board Member: Amgen, Novartis, Bristol Myers Squibb Corporate Sponsored Research: Novartis Other Substantive Relationships: Consultant, Amgen,

M. Carducci: Consultant/advisor: Amgen,

N.D. Shore: Consultant/Advisor: Amgen, Astellas, Bayer, Dendreon, Janssen, Medivation, Sanofi Corporate Sponsored Research: Amgen, Astellas, Bayer, Dendreon, Janssen, Medivation, Sanofi, Active Biotech, BMS, Millenium, Oncogenix, Progenics, BN Immunotherapeutics,

P. Sieber: Other substantive relationships: consultant, speaker: Amgen,

R. Wei: Employee and stockholder: Amgen,

C. Goessl: Employee and stockholder: Amgen.

All other authors have declared no conflicts of interest.