Abstract 685P
Background
ENZA significantly prolonged metastasis-free survival (MFS; hazard ratio [HR] 0.29; 95% CI 0.24-0.35; P < .001) (N Engl J Med. 2018;378:2465) and overall survival (OS) (HR 0.73; 95% CI 0.61-0.89; P = .001) (Presented at: the ASCO20 Virtual Scientific Program; May 29-31, 2020) in men with nmCRPC and rapidly rising PSA in PROSPER. PSA responses were significantly greater in ENZA-treated men compared with PBO (Sternberg et al. Eur Urol. 2018;17:e868). We report associations of PSA responses and progression with MFS.
Methods
Men with nmCRPC, 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 and PSA response. PSA values were obtained at week 17 and every 16 weeks thereafter.
Results
933 of 1401 enrolled men were assigned to ENZA. By week 17, 79% of ENZA-treated men had a PSA decline ≥ 50% from baseline; 23% had a PSA value < 0.2 ng/mL (Table). PSA responses were significantly associated with longer MFS. A multivariate analysis showed a PSA increase of 25% and 2 ng/mL from nadir was associated with shorter MFS in ENZA-treated men (HR 3.71; 95% CI 2.72-5.06) but not PBO-treated men (HR 1.16; 95% CI 0.61-2.20).
Conclusions
In ENZA-treated men with nmCRPC and rapidly rising PSA, PSA responses were significantly associated with longer MFS, suggesting that early changes in PSA can be used to determine if a patient has an increased risk of metastasis. Table: 685P
| PSA decline from baseline within the first 17 weeks | ENZA + ADT (n = 933) | |
| No. (%) | Median MFS, mo | |
| ≥ 50% | ||
| Yes | 737 (79) | 36.8 (34.2-NR) |
| No | 196 (21) | 22.1 (14.8-29.4) |
| HR* (95% CI) | 0.32 (0.24-0.42) | |
| ≥ 90% | ||
| Yes | 479 (51) | NR (36.0-NR) |
| No | 454 (49) | 29.0 (25.7-34.2) |
| HR* (95% CI) | 0.39 (0.30-0.52) | |
| To PSA < 0.2 ng/mL | ||
| Yes | 219 (23) | NR (NR-NR) |
| No | 714 (77) | 33.4 (29.3-36.8) |
| HR* (95% CI) | 0.24 (0.15-0.39) |
*Based on an unstratified Cox proportional model with < 1.00 favoring Yes. ADT, androgen deprivation therapy; ENZA, enzalutamide; HR, hazard ratio; MFS, metastasis-free survival; NR, not reached; PSA, prostate-specific antigen.
Clinical trial identification
NCT02003924.
Editorial acknowledgement
Editorial assistance funded by Pfizer Inc. (New York, NY) and Astellas Pharma, Inc (Northbrook, IL), the co-developers of enzalutamide, was provided by Stephanie Vadasz, PhD and Dena McWain from Ashfield Healthcare Communications.
Legal entity responsible for the study
Pfizer Inc. and Astellas Pharma, Inc.
Funding
Pfizer Inc. and Astellas Pharma, Inc.
Disclosure
M. Hussain: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (institution), Travel/Accommodation/Expenses: Astellas Pharma; Research grant/Funding (institution): PCCTC; Honoraria (institution): PER; Honoraria (institution): Projects in Knowledge; Honoraria (institution): Sanofi/Genzyme; Honoraria (institution): Phillips Gilmore Oncology; Honoraria (institution): Research to Practice; Honoraria (institution): MLI PeerView; Research grant/Funding (institution): RTP; Licensing/Royalties, Serial Number: UM-14437/US-1/PRO 60/923,385 UM-14437/US-2/ORD 12/101,753: Systems and Methods For Tissue Imaging; Licensing/Royalties, Serial Number: 224990/10-016P2/311733 61/481/671: Method Of Treating Cancer; Licensing/Royalties, Application No/Patent No. 11764665.4- 1464: Dual Inhibition of MET and VEGF for the treatment of castration resistant prostate cancer and osteoblastic bone metastases; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech. C.N. Sternberg: Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Asetllas; Advisory/Consultancy: Sanofi-Genzyme; Advisory/Consultancy: Roche-Genentech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Medscape; Advisory/Consultancy: UroToday; Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Astellas; Advisory/Consultancy: Sanofi-Genzyme; Advisory/Consultancy: Roche-Genentech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Medscape; Advisory/Consultancy: UroToday. E. Efstathiou: Research grant/Funding (self), Research grant/Funding (institution), Non-remunerated activity/ies: Astellas; Research grant/Funding (self), Research grant/Funding (institution), Non-remunerated activity/ies: Pfizer Inc.; Research grant/Funding (self), Research grant/Funding (institution), Non-remunerated activity/ies: Jannsen; Research grant/Funding (self), Research grant/Funding (institution), Non-remunerated activity/ies: Sanofi; Advisory/Consultancy, Non-remunerated activity/ies: Merck; Advisory/Consultancy, Non-remunerated activity/ies: AstraZeneca. K. Fizazi: Honoraria (institution), Advisory/Consultancy: Astellas Pharma; Honoraria (institution), Advisory/Consultancy: Janssen; Honoraria (institution), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Curevac; Honoraria (institution), Advisory/Consultancy: Orion. Q. Shen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer, Inc. X. Lin: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer, Inc. J. Sugg: Full/Part-time employment: Asetllas Pharma Inc.; Shareholder/Stockholder/Stock options: AstraZeneca. J. Steinberg: Shareholder/Stockholder/Stock options, Full/Part-time employment: Asetllas Pharma Inc. B. Noerby: Shareholder/Stockholder/Stock options, by an immediate family member: Lundbeck; Shareholder/Stockholder/Stock options, by an immediate family member: Novo Nordisk; Shareholder/Stockholder/Stock options, by an immediate family member: Teva. U. De Giorgi: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy: Astellas; Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen. N. Shore: Advisory/Consultancy: Amgen; Advisory/Consultancy: Astellas; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Dendreon; Advisory/Consultancy: Ferring; Advisory/Consultancy: Fergene; Advisory/Consultancy: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy: Myovant; Advisory/Consultancy: Nymox; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Tolmar; Advisory/Consultancy: Boston Scientific; Advisory/Consultancy: MDx Health. F. Saad: Advisory/Consultancy, Research grant/Funding (institution): Astellas ; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Myovant; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Merck.