1777P - Enzalutamide (enza) monotherapy for the treatment (tx) of prostate cancer with high-risk biochemical recurrence (BCR): EMBARK secondary endpoints

Background

The primary analysis of EMBARK demonstrated that after a median follow-up of 60.7 months metastasis-free survival for enza + leuprolide acetate (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) was clinically meaningful and statistically superior to placebo + LA. Here, we present other non-key secondary efficacy endpoints for enza monotherapy vs placebo + LA.

Methods

EMBARK (NCT02319837) is a phase 3 study of patients (pts) with high-risk 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 (RP) ± postoperative RT. Pts were randomized (1:1) to 160 mg/day enza monotherapy (open-label) or placebo + LA (LA alone). LA 22.5 mg was administered every 12 weeks. If the PSA was <0.2 ng/mL at Week 36, 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, symptomatic progression, first symptomatic skeletal event, and resumption of any hormonal therapy following tx suspension.

Results

713 pts were eligible and randomized (enza monotherapy, n=355; LA alone, n=358). Median (range) tx duration excluding tx suspension was 45.9 (0.4–88.9) months for enza monotherapy and 35.4 (0.7–85.7) months for LA alone. Time to: distant metastasis (HR 0.61; 95% CI, 0.41–0.92; p=0.0171), symptomatic progression (HR 0.62; 95% CI, 0.49–0.79; p<0.0001), and first symptomatic skeletal event (HR 0.42; 95% CI, 0.23–0.79; p=0.0057) all favored enza monotherapy vs. LA alone. Time to resumption of any hormonal therapy after tx suspension favored LA alone vs enza monotherapy (HR 1.66; 95% CI, 1.38–1.98; p<0.0001). All p-values are nominal.

Conclusions

In pts with high-risk BCR, enza monotherapy showed clinically meaningful delays in time to distant metastasis, symptomatic progression, and time to first symptomatic skeletal event vs LA alone. After tx suspension, enza monotherapy shortened time to resumption of any hormonal therapy vs LA alone. Further work is needed to understand the risks and benefits of enza monotherapy vs other options for 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

U.F.F. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, Eisai, Janssen; Financial Interests, Personal, Invited Speaker: Roche, BMS, Clovis Oncology, AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi, Roche. 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, Sikta 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. R. Tutrone: Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., Exosome Diagnostics GmbH, Myovant Sciences GmbH, Pfizer, Inc.. J.L. Bailen: Financial Interests, Institutional, Speaker, Consultant, Advisor, Consulting; honoraria; speaker's bureau: Astellas Pharma Inc., Auxillium, Bayer, Dendreon, Janssen; Financial Interests, Institutional, Speaker, Consultant, Advisor, Consulting and honoraria: Sanofi; Financial Interests, Institutional, Research Funding: Astellas Pharma Inc., Bayer, Dendreon, Janssen, Medivation, Millenium Pharmaceuticals; Financial Interests, Personal, Other, Travel, accommodation, and expenses: Astellas Pharma Inc., Bayer, Dendreon, Valeant/Dendreon. L.I. Karsh: Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., AstraZeneca, Aurora Oncology, Bayer, Daiichi Sankyo, Dendreon, Ferring, Janssen, Merck, Pfizer, Sanofi, Specialty Networks/UroGPO, Vaxiion; Financial Interests, Institutional, Speaker’s Bureau: Astellas Pharma Inc., AstraZeneca, Bayer, Janssen, Merck, Myovant Sciences, Pfizer; Financial Interests, Institutional, Research Funding: Astellas Pharma Inc., AstraZeneca, Bayer, BioExcel, BMS, Dendreon, Exact Sciences, Epizyme, FKD Therapies, KDX Pharma, Immunis.AI, Janssen, Merck, Myovant Sciences, Pfizer, Tavanta Therapeutics. M. Ramirez-Backhaus: Financial Interests, Institutional, Speaker, Consultant, Advisor, Consulting; honoraria: Astellas Pharma Inc., Bayer, Janssen; Financial Interests, Institutional, Expert Testimony: Janssen; Financial Interests, Personal, Other, Travel, accommodation, and expenses: Astellas Pharma Inc., Janssen. E. Uchio: Financial Interests, Institutional, Research Funding: Astellas Pharma Inc., AstraZeneca, Bayer, Blue Earth Diagnostics, CG Oncology, Dendreon Pharmaceuticals LLC, Exact Sciences, Lantheus, Myriad, Janssen Oncology, Merck, Myovant Sciences, Pfizer, Seagen; Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., AstraZeneca, Bayer, Blue Earth Diagnostics, CG Oncology, Dendreon Pharmaceuticals LLC, Exact Sciences, Lantheus, Myriad, Janssen Oncology, Merck, Myovant Sciences, Pfizer, Seagen. S. Supiot: Financial Interests, Institutional, Other, Honoraria: Astellas Pharma Inc., AstraZeneca, Bayer, Ferring, Ipsen, Janssen, Merck Sharp & Dohme, Novartis AAA, Takeda; Financial Interests, Institutional, Research Funding: Astellas Pharma, Inc., AstraZeneca, Bayer, Boston Scientific, Janssen, Novartis AAA, RefleXion Medical. Y. Tang, B. Rosbrook: 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.. F. Zohren: Financial Interests, Personal, Full or part-time Employment: Pfizer, Inc.; Financial Interests, Personal, Stocks/Shares: Pfizer, Inc.. N.D. Shore: Financial Interests, Institutional, Other, Grant support and consulting fees: AbbVie, Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, Clovis Oncology, Dendreon Pharmaceuticals LLC, Ferring Pharmaceuticals, GenesisCare, Janssen Oncology, Merck, Myovant Sciences, Pfizer, Sanofi-Genzyme, Tolmar Pharmaceuticals. All other authors have declared no conflicts of interest.