PROSPER: A Phase 3, Randomized, Double-Blind, Placebo (PBO)-Controlled Study of Enzalutamide (ENZA) in Men With Nonmetastatic Castration-Resistant Prostate Cancer (M0 CRPC)
Fred Saad, MD1; Karim Fizazi, MD2; Maha Hussain, MD3; Per Rathenborg, MD4; Neal Shore, MD5; Eren Demirhan, PhD, MBA6, Katharina Modelska, MD; PhD6, De Phung, BSc7, Andrew Krivoshik, MD; PhD7, Cora N. Sternberg, MD8
1Centre hospitalier de l'Université de Montréal, Montréal, QC; 2Institut Gustave Roussy, University of Paris Sud, Villejuif, France, 3Northwestern University, Chicago, IL; 4Herlev Hospital, Herlev, Denmark, 5Carolina Urologic Research Center, Myrtle Beach, SC; 6Pfizer, Inc., San Francisco, CA; 7Astellas Pharma, Inc., Northbrook, IL; 8San Camillo and Forlanini Hospitals, Rome, Italy
Introduction: Men with M0 CRPC and rapidly rising prostate-specific antigen (PSA) are at high risk of developing metastatic (M1) CRPC. ENZA improves overall survival (OS) and radiographic progression-free survival in men with M1 CRPC. We hypothesized that ENZA will improve metastasis-free survival (MFS) in men with M0 CRPC.
Methods: Eligible men with M0 CRPC, PSA doubling time ≤ 10 mo and PSA ≥ 2 ng/mL at screening continued androgen deprivation therapy (ADT) and were randomized 2:1 to ENZA 160 mg or PBO. The primary endpoint was MFS. Secondary endpoints included time to PSA progression, time to first use of new antineoplastic therapy, OS and safety.
Results: In 1401 men, ENZA significantly prolonged median MFS (36.6 mo vs 14.7 mo [P < .0001]), time to first use of new antineoplastic therapy (39.6 mo vs 17.7 mo [P < .0001]) and time to PSA progression (37.2 mo vs 3.9 mo [P < .0001]) compared to PBO (Table). In the first interim analysis of OS there was a trend in favor of ENZA (hazard ratio [HR] = 0.80; P = .1519). Median duration of treatment was 18.4 mo vs 11.1 mo for ENZA vs PBO. Adverse events (AEs) were higher with ENZA vs PBO (any grade: 87% vs 77%; grade ≥ 3: 31% vs 23%; serious: 24% vs 18%); 10% with ENZA discontinued treatment due to AE vs 8% with PBO.
Conclusions: In men with M0 CRPC and rapidly rising PSA, ENZA treatment resulted in a clinically meaningful and statistically significant 71% reduction in the risk of developing M1 CRPC or death. AEs were consistent with the established safety profile of ENZA.
© 2018 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2018 Genitourinary Cancers Symposium. All rights reserved.
| Baseline Characteristic | ENZA + ADT (n = 933) | PBO + ADT (n = 468) |
| Age, median, y | 74 | 73 |
| PSA doubling time < 6 mo, no. (%) | 715 (77) | 361 (77) |
| Serum PSA, ng/mL | 11.1 | 10.2 |
| Endpoint | ||
| MFS,a median (95% CI), mo | 36.6 (33.1-NR) | 14.7 (14.2-15.0) |
| HR (95% CI) | 0.29 (0.24-0.35) | |
| P value | < .0001 | |
| Time to first use of new antineoplastic therapy,a median (95% CI), mo | 39.6 (37.7-NR) | 17.7 (16.2-19.7) |
| HR (95% CI) | 0.21 (0.17-0.26) | |
| P value | < .0001 | |
| Time to PSA progression,a median (95% CI), mo | 37.2 (33.1-NR) | 3.9 (3.8-4.0) |
| HR (95% CI) | 0.07 (0.05-0.08) | |
| P value | < .0001 | |
| OS,b median (95% CI), mo | NR (NR-NR) | NR (NR-NR) |
| HR (95% CI) | 0.80 (0.58-1.09) | |
| P value | .1519 | |
| aFinal analysis; binterim analysis CI, confidence interval; NR, not reached | ||
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