Enzalutamide (enza) with or without leuprolide in patients (pts) with high-risk biochemically recurrent (hrBCR) prostate cancer (PC): EMBARK post hoc analysis by age

BackgroundPts diagnosed with PC aged >70 years (y) are at greater risk of PC-related death vs pts diagnosed aged ≤70 y. In EMBARK, enza ± leuprolide significantly prolonged metastasis-free survival (MFS) by blinded independent central review vs leuprolide alone in pts with PC and hrBCR. Here, we present a post hoc analysis of outcomes by age.MethodsEMBARK, a phase 3 trial (NCT02319837), included pts after local therapy with hrBCR: 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 randomised (1:1:1) to enza + leuprolide (combo), leuprolide alone, or enza monotherapy (mono). A post hoc analysis of MFS and safety by median age in EMBARK was conducted (<70 vs ≥70 y).ResultsIn total, 543 pts (50.8%) were aged <70 y and 525 pts (49.2%) were ≥70 y. Pts aged <70 y had lower baseline PSA, a higher Gleason score group, and more prior RP vs pts aged ≥70 y across treatment (tx) groups. Compared with leuprolide alone, enza combo improved MFS in both age groups; similar trends were seen with enza mono (Table). Treatment effect in MFS was not statistically different between age groups for both tx group comparisons. Overall, median tx suspension duration was similar for pts aged <70 and ≥70 y for enza combo and enza mono, but shorter for pts <70 vs ≥70 y for leuprolide alone. Serious adverse events (AEs) were more common in pts aged ≥70 y vs <70 y for enza combo (45.0% vs 25.3%), leuprolide alone (36.2% vs 27.1%), and enza mono (43.9% vs 30.4%). Tx-related serious AEs were more common in pts aged ≥70 vs <70 y, but low overall. Table: 1638P <70 y (n=543) ≥70 y (n=525) Enza combo(n=184) Leuprolide alone(n=178) Enza mono(n=181) Enza combo(n=171) Leuprolide alone(n=180) Enza mono(n=174) MFS, median (95% CI), months NR (NR, NR) 85.1 (85.1, NR) NR (NR, NR) NR (NR, NR) NR (80.1, NR) NR (NR, NR) HR (95% CI) 0.37 (0.22, 0.62) – 0.67 (0.43, 1.05) 0.50 (0.30, 0.81) – 0.61 (0.39, 0.97) Nominal P valuea <0.0001 – 0.0790 0.0039 – 0.0342 aSubgroup analyses are underpowered. Due to small sample size, results should be interpreted with caution. P-values for the interaction between treatment and age were P=0.4200 (combo) and P=0.8039 (mono).CI, confidence interval; HR, hazard ratio; MFS, metastasis-free survival; NR, not reached; y, years. ConclusionsIn this post hoc analysis from EMBARK, similar treatment benefits for enza combo and mono vs leuprolide alone were seen in pts with hrBCR aged <70 and ≥70 y. Tx-related serious AEs were more common in older pts, but were low regardless of age.Clinical trial identificationNCT02319837.Editorial acknowledgementMedical writing and editorial support was provided by Adam Anazim, BSc, and Rosie Henderson, MSc, of Onyx (a division of Prime, London, UK) funded by Pfizer Inc. and Astellas Pharma Inc., co-developers of enzalutamide.Legal entity responsible for the studyPfizer Inc. and Astellas Pharma Inc.FundingThe study was sponsored by Pfizer Inc. and Astellas Pharma Inc., the co-developers of enzalutamide.DisclosureN.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Cold Genesys, Dendreon, Exact Imaging, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, Sanofi Genzyme, Speciality Networks, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Asieris, Alessa Therapeutics, Arquer, Fize medical, GConcology, Guardant, Ferring, Foundation Medicine, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Promaxo, Protara, Accord, Antev, Aura biosciences, Sumitomo; Financial Interests, Personal, Member of Board of Directors: Photocure, Alessa Theraputics; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Bayer, Aura, Exact Imaging, Janssen, Merck, Myovant, Novartis, Pfizer, Propella, Bristol Myers Squibb, Dendreon, Pfizer, Urogen; Financial Interests, Institutional, Local PI: Alessa, GC Oncology, FORMA therapeutics, Pacific Edge, Point Biopharma, The MT group, Theralase, Verity, Astellas, Palette Life Sciences, Steba, Zenflow. U. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, EISAI, Janssen; Financial Interests, Personal, Invited Speaker: Roche, BMS, Astrazeneca, Merck; Financial Interests, Institutional, Research Grant: Astrazeneca, Sanofi, Roche. M.E. Gleave: Financial Interests, Personal, Stocks or ownership: OncoGenex Technologies, Sustained Therapeutics, Sikta Pharmaceuticals; Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma Inc., AstraZeneca, Bayer, GDx, Johnson & Johnson Innovative Medicine (formerly Janssen), Sanofi, Pfizer Inc., Roche; Financial Interests, Personal, Other, Holds patents for OGX-011, OGX-427, ST-CP, and ST-POP: OGX-011, OGX-427, ST-CP, and ST-POP. M. Kalac: Financial Interests, Institutional, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. Y. Tang: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc.; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. R. Croitoru: Financial Interests, Personal, Full or part-time Employment: Astellas Pharma Inc.; Financial Interests, Personal, Stocks/Shares: Astellas Pharma Inc. M. Rosales: Financial Interests, Institutional, Full or part-time Employment, Current employer: Astellas Pharma; Financial Interests, Institutional, Other, Current Employer: Astellas Pharma; Non-Financial Interests, Member: ASCO. M. Huynh: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: Knight Therapeutics. I. Jan de Jong: Financial Interests, Personal, Other, educational speakers fee: Bayer, AstraZeneca. F.M. Carcano: Financial Interests, Personal, Invited Speaker, Small group updating meeting in Brazil: Adium, Janssen, Ipsen. S.J. Freedland: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Pfizer, Astellas, Janssen, Bayer, Myovant, Sanofi, Novartis, Eli Lilly. All other authors have declared no conflicts of interest.