1778P - Treatment (tx) of high-risk biochemically recurrent prostate cancer with enzalutamide (enza) in combination with leuprolide acetate (LA): Secondary endpoints from EMBARK

Background

In the phase 3 EMBARK trial, after a median follow-up of 60.7 months, enza + LA (HR 0.42; 95% CI, 0.30–0.61; p<0.0001) and enza monotherapy (HR 0.63; 95% CI, 0.46–0.87; p=0.0049) demonstrated statistically superior and clinically meaningful improvements in metastasis-free survival vs placebo (pbo) + LA. Here, we present other non-key secondary efficacy endpoints for enza + LA vs pbo + LA.

Methods

EMBARK (NCT02319837) is a study of patients (pts) with high-risk biochemical recurrence (BCR): prostate-specific antigen (PSA) doubling time ≤9 months and PSA ≥2 ng/mL above nadir post-radiotherapy (RT) or ≥1 ng/mL after radical prostatectomy ± postoperative RT. Pts were double-blinded and randomized (1:1) to enza 160 mg/day + LA or pbo + LA (LA alone). LA 22.5 mg was administered every 12 weeks. If the PSA at Week 36 was <0.2 ng/mL, tx was suspended at Week 37 and restarted when PSA was ≥2 ng/mL for pts with primary RP, and ≥5 ng/mL for pts without RP. Secondary endpoints included time to: distant metastasis, resumption of any hormonal therapy after tx suspension, castration resistance, symptomatic progression, and first symptomatic skeletal event.

Results

713 pts were eligible and randomized into the study (enza + LA, n=355; LA alone, n=358). Median (range) tx duration excluding tx suspension was 32.4 (0.1–83.4) months for enza + LA and 35.4 (0.7–85.7) months for LA alone. Time to: distant metastasis (HR 0.44; 95% CI, 0.28–0.69; p=0.0002), resumption of any hormonal therapy after tx suspension (HR 0.69; 95% CI, 0.58–0.83; p<0.0001), castration resistance (HR 0.09; 95% CI, 0.05–0.16; p<0.0001), symptomatic progression (HR 0.55; 95% CI, 0.43–0.70; p<0.0001), and first symptomatic skeletal event (HR 0.26; 95% CI, 0.13–0.55; p=0.0001) favored enza + LA vs LA alone. All p-values are nominal.

Conclusions

In pts with high-risk BCR, enza + LA vs LA alone demonstrated clinically meaningful delays in time to: distant metastasis, resumption of any hormonal therapy after tx suspension, castration resistance, symptomatic progression, and first symptomatic skeletal event. If approved, enza combination may represent a new standard of care for pts with high-risk BCR.

Clinical trial identification

NCT02319837.

Editorial acknowledgement

Medical writing and editorial support were provided by Isabel Aitcheson, BSc, and Sinead Stewart, of Onyx (a Prime Global agency) funded by Pfizer, Inc. and Astellas Pharma, Inc., co-developers of enzalutamide.

Legal entity responsible for the study

Pfizer, Inc. and Astellas Pharma, Inc.

Funding

Pfizer, Inc. and Astellas Pharma, Inc.

Disclosure

S.J. Freedland: Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., Pfizer, Janssen, Bayer, Sanofi, Dendreon, Myovant, AstraZeneca, Merck. M.E. Gleave: Financial Interests, Institutional, Stocks or ownership: OncoGenex Technologies, Sustained Therapeutics, Sitka Pharmaceuticals; Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., AstraZeneca, Bayer, GDx, Janssen, Sanofi, Pfizer, TerSera, Roche; Financial Interests, Institutional, Other, Holds patents for OGX-011: OGX-011; Financial Interests, Institutional, Other, Holds patents for OGX-427: OGX-427; Financial Interests, Institutional, Other, Holds patents for ST-CP: ST-CP; Financial Interests, Institutional, Other, Holds patents for ST-POP: ST-POP. U.F.F. De Giorgi: Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., Bayer, BMS, Ipsen, Janssen, Novartis, Pfizer, Sanofi, PharmaMar; Financial Interests, Institutional, Research Funding: AstraZeneca, Roche, Sanofi; Financial Interests, Personal, Funding, Travel funds: BMS, Ipsen, Janssen, Pfizer, Roche. A. Rannikko: Financial Interests, Institutional, Advisory Board: Bayer, Janssen, Orion Pharma; Financial Interests, Institutional, Leadership Role, Board chair: Orion Research Foundation; Financial Interests, Institutional, Member of Board of Directors: Ida Montin Research Foundation. C. Pieczonka: Financial Interests, Institutional, Speaker, Consultant, Advisor: AstraZeneca, Bayer, Blue Earth, CellVax, Dendreon, Eli Lilly, Janssen, Merck, Myovant Sciences, Pfizer, Daiichi Sankyo, Sun; Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Bayer, Dendreon, Janssen, Merck, Myovant Sciences, Sun; Financial Interests, Institutional, Other, Honoraria; received equipment, materials, drugs, medical writing, gifts or other services: Astellas Pharma Inc., Pfizer. K. Brasso: Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., Bayer, Janssen, Merck Sharp & Dohme, Novartis. H. Woo: Financial Interests, Institutional, Speaker, Consultant, Advisor, Consultant and shareholder: Prospection Party Ltd; Financial Interests, Institutional, Advisory Board, Advisory board member and has received honoraria: Astellas Pharma Inc.; Financial Interests, Institutional, Other: Bayer, Boston Scientific, Cipla, Janssen; Financial Interests, Institutional, Member of Board of Directors: Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Australasian Urological Foundation, Australasian College of Surgeons, Urological Society of Australia and New Zealand. A. Gomez Caamaño: Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., Bayer, Janssen; Financial Interests, Institutional, Funding, Institutional funding: Astellas Pharma Inc.; Financial Interests, Institutional, Other, Honoraria: Astellas Pharma Inc., AstraZeneca, Bayer, Janssen; Financial Interests, Personal, Other, Travel expenses: Astellas Pharma Inc., Bayer, Janssen. Y. Tang, B. Rosbrook, F. Zohren: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. G.P. Haas, M. Rosales: Financial Interests, Personal, Full or part-time Employment: Astellas Pharma, Inc.; Financial Interests, Personal, Stocks/Shares: Astellas Pharma, Inc.. N.D. Shore: Financial Interests, Institutional, Research Funding: AbbVie, Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, BMS, Dendreon, Exact Sciences, Ferring, FerGene, Janssen, MDx Health, Merck, Myovant, Nymox, Pfizer, Sanofi, Tolmar. All other authors have declared no conflicts of interest.