Introduction:
In the STRIVE trial, ENZA significantly reduced the risk of prostate cancer progression-free survival compared with BIC in a cohort of patients with both metastatic and nonmetastatic CRPC, (J Clin Oncol. 34:2098-2106). However, patients with nmCRPC in various global regions are frequently treated with BIC rather than ENZA in this early disease setting. To better illustrate the clinical benefit of ENZA compared with BIC, here we present data from the nmCRPC cohort from the STRIVE study.
Methods:
In this randomized, double-blind, phase 2 study, patients with CRPC were randomly assigned to ENZA 160 mg per day or BIC 50 mg per day, stratified by disease stage, with androgen deprivation therapy continued in both arms. The primary endpoint was progression-free survival (PFS) defined as time from randomization to PSA progression by PCWG2 criteria, radiographic progression, or death due to any cause. Key secondary endpoints included time to PSA progression (TTPP). Kaplan-Meier curves and medians were calculated and hazard ratios (HRs) estimated by using a Cox regression model. Safety data were also determined for the nmCRPC subset and not adjusted for time on study drug. The nmCRPC subgroup of STRIVE enrolled 70 patients in the ENZA arm and 69 patients in the BIC arm.
Results:
Baseline nmCRPC patient characteristics were generally comparable between cohorts: median age (years): ENZA 74, BIC 77; baseline ECOG 0/1 (%): ENZA 80/20, BIC 77/23; M0/N0:M0/N1 status (%): ENZA 87:13, BIC 87:13; median PSA doubling time (months): ENZA 3.9, BIC 5.3. At 17 months median follow-up, ENZA reduced risk of progression or death by 76% versus BIC in nmCRPC patients (HR, 0.24; 95% CI, 0.14-0.42; P < .0001; Figure). PFS benefit from ENZA treatment was observed across all subgroups, including age (<75, ≥75), ECOG (0, 1), and Gleason Score (≤7, >8). ENZA reduced risk of PSA progression by 82% versus BIC in nmCRPC patients (HR, 0.18; 95% CI, 0.10-0.34; P < .0001; Figure). The most frequent nmCRPC adverse events in the ENZA arm (vs. BIC [%]): fatigue (36.2 vs. 21.7), hot flush (20.3 vs. 2.9), decreased appetite (17.4 vs. 5.8), dizziness (17.4 vs. 4.3), and nausea (17.4 vs. 13.0).
Conclusion:
Improved clinical benefit with ENZA versus BIC was observed in patients with nmCRPC from the STRIVE trial, as illustrated by the Kaplan-Meier curves of PFS and TTPP. Improved ENZA PFS benefit compared with BIC was supported across all nmCRPC patient subgroups. The safety profile of ENZA in this nmCRPC subset is consistent with the overall CRPC population in STRIVE and the overall safety profile of ENZA across studies. Although this nmCRPC study cohort is limited by a relatively small number of patients, these results are consistent with the clinical benefit of ENZA compared with placebo, as demonstrated in the phase 3 PROSPER trial of nmCRPC patients. ENZA is the only novel hormone therapy with demonstrated clinical benefit versus BIC across prostate cancer disease states, including metastatic hormone-sensitive prostate cancer, nmCRPC, and mCRPC.
Funding: Pfizer Inc. and Astellas Pharma, Inc.
Image(s) (click to enlarge):
ENZALUTAMIDE (ENZA) VERSUS BICALUTAMIDE (BIC) IN PATIENTS WITH NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER (nmCRPC): STRIVE TRIAL EFFICACY AND SAFETY DATA
Category
Prostate Cancer > CRPC
Description
Poster #133
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Presented By: Celestia S. Higano
Authors:
David F. Penson
Andrew J. Armstrong
Raoul S. Concepcion
Neeraj Agarwal
Carl A. Olsson
Lawrence I. Karsh
Curtis J. Dunshee
William Duggan
Qi Shen
Jennifer Sugg
Gabriel P. Haas
Celestia S. Higano