Abstract 3709
Background
Men with M0 CRPC are at high risk of developing metastatic (M1) CRPC. The goal of M0 CRPC treatment is to delay M1 disease progression, delay additional antineoplastic therapies, and ultimately prolong survival and maintain quality of life. In the primary analysis of PROSPER, ENZA improved metastasis-free survival (MFS) in men with M0 CRPC. Here we report results in subgroups of patients (pts) by age and region.
Methods
Eligible men with M0 CRPC, prostate-specific antigen (PSA) doubling time ≤ 10 mo and PSA ≥ 2 ng/mL at screening continued androgen deprivation therapy 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, overall survival, and safety.
Results
1401 men were enrolled with a median age of 74 y (standard deviation, 7.8 y). Baseline characteristics were generally similar across regions and age groups (Table). Baseline use of bone-targeting agents was higher in North America compared with the other 2 regions. A greater proportion of pts aged ≥ 75 y had and ECOG PS of 1 than pts aged < 75 y. In all men, ENZA reduced the risk of metastasis or death by 71% (HR, 0.29; 95% CI, 0.24-0.35; P < 0.0001). The risk reduction with ENZA use was similar across all subgroups (Table). Safety results were generally similar among all subgroups, except that more pts in the group aged ≥ 75 y reported adverse event as the primary reason for discontinuation (13% with ENZA vs 10% with PBO) than in the overall pt population (9% with ENZA vs 6% with PBO), and more pts in North America reported falls (15%) than in Europe (7%) or rest of world (10%).Table: 805P
| Overall (N = 1401) | Age < 75 y (n = 756) | Age ≥ 75 y (n = 645) | Europe (n = 690) | Rest of world (n = 507) | North America (n = 204) | |
|---|---|---|---|---|---|---|
| Baseline characteristics | ||||||
| Age category, no. (%) < 65 y 65 to < 75 y ≥ 75 y | 190 (14) 566 (40) 645 (46) | 190 (25) 566 (75) 0 | 0 0 645 (100) | 100 (15) 285 (41) 305 (44) | 57 (11) 200 (40) 250 (49) | 33 (16) 81 (40) 90 (44) |
| ECOG PS, no. (%) 0 1 | 1129 (81) 270 (19) | 668 (88) 87 (12) | 461 (72) 183 (28) | 555 (80) 134 (19) | 401 (79) 105 (21) | 173 (85) 31 (15) |
| Use of bone-targeting agent, no. (%) Yes | 153 (11) | 77 (10) | 76 (12) | 74 (11) | 36 (7) | 43 (21) |
| PSA doubling time, median (range), mo | 3.7 (0.4-71.8) | 3.5 (0.6-28.9) | 4.0 (0.4-71.8) | 3.9 (0.4-71.8) | 3.5 (0.4-10.0) | 3.7 (0.5-14.7) |
| PSA doubling time < 6 mo, no. (%) | 1076 (77) | 596 (79) | 480 (74) | 510 (74) | 411 (81) | 155 (76) |
| Efficacy | ||||||
| MFS HR (95% CI) P value | 0.29 (0.24-0.35) < 0.0001 | 0.25 (0.20-0.33) < 0.0001 | 0.35 (0.26-0.47) < 0.0001 | 0.24 (0.18-0.32) < 0.0001 | 0.32 (0.23-0.43) < 0.0001 | 0.41 (0.25-0.66) < 0.0001 |
Abbreviation: ECOG PS, Eastern Cooperative Oncology Group Performance Status.
Conclusions
In men with M0 CRPC and rapidly rising PSA, ENZA treatment resulted in a clinically meaningful and statistically significant reduction of developing metastases or death. Results were consistent across subgroups of pts by age and geographic region.
Clinical trial identification
NCT02003924.
Legal entity responsible for the study
Pfizer, Inc. and Astellas Pharma, Inc.
Funding
Pfizer, Inc. and Astellas Pharma, Inc.
Editorial Acknowledgement
Medical writing and editorial support, funded by Pfizer Inc., and Astellas Pharma, Inc., was provided by Stephanie Vadasz, Ph.D., and Shannon Davis of Ashfield Healthcare Communications.
Disclosure
K. Fizazi: Honoraria, consultant: Amgen, Astellas, Bayer, Clovis, CureVac, Janssen, Orion, Sanofi. M. Hussain: Honoraria: Sanofi, OncLive; Travel expenses: Sanofi; Institutional research funding: AstraZeneca, Pfizer, Bayer, Genentech. F. Saad: Honoraria, institutional research funding, consultant: Janssen, Sanofi, Astellas, Bayer, Pfizer. N. Shore: Consultant: Amgen, Astellas, Bayer, Dendreon, Fleming, Janssen, Medivation, Tolmar; Participated in speakers' bureaus: Janssen, Bayer, Dendreon. U. De Giorgi: Honoraria, consultant: Astellas, Bristol-Myers Squibb, Ipsen, Janssen, Pfizer, Novartis, Sanofi. E. Efstathiou: Honoraria, research funding, advisory boards: Janssen, Sanofi, Tolmar, Pfizer, Medivation, Astellas, Bayer, AstraZeneca. M. Al-Adhami, K. Modelska: Employees: Pfizer Inc. D. Phung, J. Steinberg: Astellas, Inc. C.N. Sternberg: Honoraria, institutional research funding: Pfizer, Astellas, Sanofi, Janssen, Bayer, Clovis Oncology, Ferring. All other authors have declared no conflicts of interest.