Presentation Authors: Fred Saad*, Montreal, QC, Neal D. Shore, Myrtle Beach, SC, Karim Fizazi, Villejuif, France, Joyce Steinberg, Janet Kim, Northbrook, IL, Ping Lin, Katharina Modelska, San Francisco, CA, Tomasz M. Beer, Portland, OR
Introduction: Enzalutamide (ENZA) prolongs radiographic progression-free survival (rPFS) and overall survival (OS) in men with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC are at high risk of developing bone metastases; skeletal complications of bone metastases contribute to morbidity, pain, and death. In this exploratory post hoc analysis of PREVAIL, we analyzed clinical outcomes associated with bone-targeted therapies (BTT) and ENZA vs. ENZA alone.
Methods: The Phase 3 PREVAIL study (NCT01212991) randomized men with mCRPC 1:1 to ENZA (160 mg) or placebo (PBO) with continued androgen-deprivation therapy. Target population for this post hoc analysis was men with bone metastases at baseline, grouped by pre-study baseline BTT use. Co-primary endpoints were rPFS and OS. Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration was defined as time from randomization to first evidence of ECOG PS deterioration by â‰¥1 grade. Results are presented as hazard ratio (HR) (95% confidence interval [CI]).
Results: Of 1429 men, 410 had pre-study BTT use (ENZA, n=534; ENZA + BTT, n=206; PBO, n=485; PBO + BTT, n=204). The risk of rPFS was similar between ENZA + BTT and ENZA alone (HR [95% CI]=1.05 [0.69, 1.60], p=0.4408), whereas the risk of death was higher in ENZA + BTT vs. ENZA alone (1.44 [1.08, 1.92], p=0.0076) (Table). There was a 31% reduction in the risk of rPFS in PBO + BTT vs. PBO alone (0.69 [0.52, 0.93], p=0.0075), and the risk of death was similar between PBO + BTT and PBO alone (0.90 [0.69, 1.19], p=0.2669). The risk of ECOG PS deterioration was similar between ENZA + BTT and ENZA alone (1.06 [0.84, 1.33], p=0.6367), and between PBO + BTT and PBO alone (0.94 [0.74, 1.20], p=0.3615).
Conclusions: In men from PREVAIL with bone metastases at baseline, pre-study BTT use with ENZA was not associated with improved clinical outcomes vs. ENZA alone. rPFS was improved in men taking PBO + BTT vs. PBO alone. The results of these exploratory analyses suggest that BTTs do not improve outcomes in combination with first-line ENZA in mCRPC. Further analysis of optimal timing and combinations when using BTTs remains relevant.
Source of Funding: This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Medical writing assistance was provided by Patrick Gonyo, PhD, and editorial assistance was provided by Jane Beck from Complete HealthVi