1792P - Effects of enzalutamide on overall survival +/- early docetaxel in participants aged less than 70 yrs versus greater than or equal to 70 yrs in ENZAMET (ANZUP 1304)

Background

Enzalutamide (ENZA) and abiraterone are standard of care for people with metastatic hormone-sensitive prostate cancer (mHSPC). It is important to understand the benefits of these agents in older patients, who may be more frail and have more co-morbidities. In this post-hoc analysis, we assessed the efficacy of ENZA in patients with mHSPC ≥70yrs vs <70yrs of age.

Methods

ENZAMET randomly assigned participants (pts) with mHSPC to treatment with testosterone suppression (TS) plus either a non-steroidal anti-androgen (NSAA) or enzalutamide (ENZA). Stratification factors included age, volume of disease (high vs low), and planned use of concurrent docetaxel (DTX) as agreed by the participant and the treating physician. The same methods were used for overall survival (OS) analysis as in the full trial. Quality of Life (QoL) and safety analyses by age ≥70yrs vs <70yrs are ongoing.

Results

Of 1125 pts randomised, 514/1125 (46%) were aged ≥70yrs. The rate of DTX usage was lower in pts aged ≥70yrs (35% vs 52%). The beneficial effects of ENZA on OS seen in the whole cohort are maintained in pts aged ≥70yrs, regardless of planned use of early DTX (Table). Pts aged ≥70yrs treated with ENZA had a significant improvement in OS (Table) in line with younger pts.

Table: 1792P

Hazard ratios (HR) and confidence intervals (CI) for effects of ENZA vs NSAA on OS in subgroups according to age and planned DTX

Conclusions

This post-hoc analysis demonstrates that pts aged ≥70 yrs treated with ENZA/TS +/- DTX have similar benefical treatment effects to the overall cohort. These data suggest ENZA is a suitable option for older men with mHSPC fit for enzalutamide.

Clinical trial identification

NCT02446405.

Editorial acknowledgement

Legal entity responsible for the study

The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP).

Funding

Astellas and Cancer Australia.

Disclosure

L.G. Horvath: Financial Interests, Personal, Advisory Board, Honorarium donated back to Chris O'Brien Lifehouse (My hospital): Imagion Biosystems; Financial Interests, Institutional, Invited Speaker: Astellas, Janssen, Amgen; Financial Interests, Institutional, Advisory Board: Astellas, Bayer; Financial Interests, Personal, Member of Board of Directors, No payment: ANZUP (Australia and New Zealand Urogenital and Prostate) Clinical Trials Group; Financial Interests, Personal, Stocks/Shares, Stock options: Imagion Biosystems; Financial Interests, Personal, Stocks/Shares: My Emergency Doctor; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Local PI, MK7684-001MK3475-991: MSD; Financial Interests, Institutional, Local PI, AMG160 Phase 1AMG509 Phase 1AMG757 Phase 1: Amgen; Financial Interests, Institutional, Local PI, 9785-CL-0335 (ARCHES): Astellas; Financial Interests, Institutional, Local PI, SHR3680-002: Jiangsu Hengrui Medicines; Financial Interests, Institutional, Local PI, TALAPRO2, TALAPRO3: Pfizer; Financial Interests, Institutional, Local PI, CYCLONE-2, CYCLONE-3: Eli Lilly; Financial Interests, Institutional, Steering Committee Member, ENZAMET, ENZARAD, DASL-HiCAP, GUIDE, ANZAdapt: ANZUP; Financial Interests, Institutional, Local PI, GALAHADACISPrevalence: Janssen Cilag; Financial Interests, Institutional, Local PI, GSK204697: GSK; Financial Interests, Institutional, Local PI, XL184-021: Exelexis; Financial Interests, Institutional, Local PI, BGB-A317BGB-283BGB-A317-290: BeiGene; Financial Interests, Institutional, Local PI, FPT155-001: Five Prime; Financial Interests, Institutional, Local PI, AB928CSP0003: ARCUS; Financial Interests, Institutional, Local PI, ATG-017 and ATG-019: Antagene; Financial Interests, Institutional, Local PI, JANUX007: Janux; Financial Interests, Institutional, Local PI, Petranha: AstraZeneca; Financial Interests, Institutional, Local PI, HP-518-CS-001: Hinova; Financial Interests, Institutional, Local PI, ENZAMET, ENZA-P, Upfront PSMA, ANZAdapt, GUIDE: ANZUP. I.D. Davis: Financial Interests, Personal, Full or part-time Employment, Professor of Medicine and Head of Eastern Health Clinical School: Monash University; Financial Interests, Personal, Full or part-time Employment, Professor of Medicine; Head, Eastern Health Clinical School; medical oncologist: Eastern Health; Financial Interests, Personal, Royalties, Authorship royalties for: Health Press; Financial Interests, Personal, Other, Remuneration for associate editor role in Therapeutic Advances in Medical Oncology: SAGE; Financial Interests, Institutional, Local PI, Institutional support for clinical research: Movember Foundation, Merck/MSD, BMS, Exelixis, Astellas, Pfizer, AstraZeneca, Roche/Genentech, Eisai, Bayer, Janssen, Ipsen, Seagen; Non-Financial Interests, Member of Board of Directors, Director and Chair: ANZUP Cancer Trials Group; Non-Financial Interests, Advisory Role, All honoraria and payments are made directly to ANZUP Cancer Trials Group with no pass-through payment: Roche, Eisai, Pio Therapeutics, Xennials Therapeutics, Telix Therapeutics; Non-Financial Interests, Other, Member of Council: Clinical Oncology Society of Australia; Non-Financial Interests, Member: ASCO, Clinical Oncology Society of Australia, Medical Oncology Group of Australia, American Association for Cancer Research, Australian Academy of Health and Medical Sciences. R. Zielinski: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca; Financial Interests, Institutional, Research Funding: BMS, AstraZeneca, Roche. A. Thomson: Financial Interests, Personal, Invited Speaker: Novartis, Roche, Exact Sciences, Lilly, Gilead; Financial Interests, Personal, Advisory Board: Novartis, MSD, Amgen; Other, Other, Support for attending conference: Novartis, MSD. S.K. Sandhu: Financial Interests, Institutional, Advisory Board, I have served on advisory boards for BMS. The contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: BMS; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for MSD. The e contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Merck Sharp and Dohme; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for AstraZeneca. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: AstraZeneca; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for Novartis. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Novartis; Financial Interests, Institutional, Advisory Board, I have served on an advisory board for Merck Serono. The contracts for my service are set up with the institution and funds go into a research fund at the Peter MacCallum Cancer Centre: Merck Serono; Financial Interests, Institutional, Research Grant, My institution receives grant funding to run an investigator initiated trial that I lead: Novartis, Genentech, Amgen, AstraZeneca, Merck Serono, Merck Sharp and Dohme; Financial Interests, Institutional, Funding, Pfizer are providing funding to my institution for the conduct of an investigator initiated clinical trial: Pfizer; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Janssen sponsored studies and don't receive any renumeration for this: Janssen; Non-Financial Interests, Principal Investigator, I am a principal investigator on several Novartis sponsored studies and don’t receive any renumeration for this: Novartis; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Genentech sponsored studies and don't receive any renumeration for this: Genentech; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of BMS sponsored studies and don't receive any renumeration for this: BMS; Non-Financial Interests, Other, I serve on the Independent Safety and Data Monitoring committee for 2 of Novartis sponsored studies and don’t receive any compensation for this: Novartis; Non-Financial Interests, Principal Investigator, I am the Principal Investigator for several AstraZeneca sponsored studies and am not remunerated for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for several Janssen sponsored trials and i do not receive compensation for this: Janssen; Non-Financial Interests, Other, I serve on the steering committee for one AstraZeneca sponsored trial and I do not receive compensation for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for one Genentech sponsored trials and I do not receive compensation for this: Genentech; Non-Financial Interests, Other, I serve on the steering committee for a BMS sponsored trial and I do not receive renumeration for this: BMS. M.N. Reaume: Financial Interests, Personal, Advisory Board: Ipsen, Pfizer, EMD Serono, Novartis. D. Pook: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: BMS, MSD, Ipsen, Pfizer, Eisai, Astellas; Financial Interests, Institutional, Local PI: BMS, Astellas, Roche, MSD, Amgen; Financial Interests, Institutional, Coordinating PI: Pfizer, Ipsen. F. Parnis: Financial Interests, Personal, Invited Speaker: Bayer. S. North: Financial Interests, Personal, Advisory Board, honoraria: Astellas, BMS, Janssen, Merck, Roche, Sanofi, Bayer, AstraZeneca; Financial Interests, Institutional, Local PI, per case funding: Sanofi, AstraZeneca, Ipsen, Astellas. K.N.N. Chi: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Point Biopharma, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Janssen, Novartis, Roche; Financial Interests, Institutional, Trial Chair: AstraZeneca, Arvinas, Janssen, Novartis; Financial Interests, Institutional, Local PI: Arvinas. M.R. Stockler: Financial Interests, Institutional, Research Grant, DASL: Bayer; Financial Interests, Institutional, Research Grant, ENZAMET & ENZARAD: Astellas; Financial Interests, Institutional, Research Grant, KEYPAD: Amgen, MSD; Financial Interests, Institutional, Research Grant, NIVORAD: BMS; Financial Interests, Institutional, Research Grant: Pfizer, Roche; Financial Interests, Institutional, Research Grant, ADELE: BeiGene; Financial Interests, Institutional, Research Grant, PARAGON2: Novartis; Financial Interests, Institutional, Other, Study Drug for Cannabis CINV Trial: Tilray. C. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Genentech Roche, Bayer, Astellas, Pfizer, Pfizer, Sanofi, Lilly; Financial Interests, Personal, Other, Consultancy: Janssen; Financial Interests, Personal, Advisory Board: Point, Cellcentric; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Institutional, Research Grant: Bayer, Janssen, Astellas, Pfizer, Dendreon, Sanofi. All other authors have declared no conflicts of interest.