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E-Poster Display

685P - A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC): Outcomes by prostate-specific antigen (PSA) response

Date

17 Sep 2020

Session

E-Poster Display

Presenters

Maha Hussain

Citation

Annals of Oncology (2020) 31 (suppl_4): S507-S549. 10.1016/annonc/annonc275

Authors

M. Hussain1, C.N. Sternberg2, E. Efstathiou3, K. Fizazi4, Q. Shen5, X. Lin6, J. Sugg7, J. Steinberg8, B. Noerby9, U. De Giorgi10, N. Shore11, F. Saad12

Author affiliations

  • 1 Department Of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 60611 - Chicago/US
  • 2 Department Of Hematology And Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York/US
  • 3 Department Of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston/US
  • 4 Department Of Cancer Medicine, University of Paris Saclay, Villejuif/FR
  • 5 Department Of Global Clinical Development, Pfizer Inc., Collegeville/US
  • 6 Department Of Biostatistics, Pfizer Inc., La Jolla/US
  • 7 Department Of Biostatistics, Astellas Pharma, Inc., Northbrook/US
  • 8 Department Of Medical Oncology, Astellas Pharma, Inc., Northbrook/US
  • 9 Department Of Urology, Sygehus, Lillebaelt, Vejle/DK
  • 10 Department Of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST IRCCS, Meldola/IT
  • 11 Department Of Urology, Carolina Urologic Research Center, Myrtle Beach/US
  • 12 Department Of Medical Oncology, University of Montreal Hospital Center, Montreal/CA
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Resources

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.

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