Clinical prognostic factors within the high volume subgroup of metastatic hormone sensitive prostate cancer (mHSPC) in ENZAMET (ANZUP 1304)

BackgroundPatients (pts) with HV mHSPC have poorer outcomes than pts with low volume (LV) disease, despite improved overall survival (OS) with enzalutamide (ENZA) in both subgroups. We hypothesised that intrinsic tumour features and metastatic bone burden further refine disease risk within this subgroup.MethodsParticipants in ENZAMET received testosterone suppression (TS) plus non-steroidal anti-androgen or TS plus ENZA. Post-hoc analyses of T-stage, Gleason score (GS), visceral metastases (mets), and bone burden (BB) were performed in the following subgroups: M1(synchronous)-HV, M0(metachronous)-HV, and M1-LV. High BB was defined by the upper quartile of alkaline phosphatase (ALP) at trial enrolment; BB analyses excluded pts with visceral mets. Endpoints were OS, prostate cancer specific survival (PCSS), and PSA progression-free survival (PSA-PFS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by univariable Cox models.ResultsThe table summarises OS in HV groups. In M1-HV, 179/344 (52%) had high BB (ALP>150 IU/L) which was associated with shorter OS (HR 1.64, p<0.001) along with high GS (HR 1.80, p=0.01), but not T-stage; similar findings were seen for PCSS and PSA-PFS (not GS for latter). In M0-HV, high BB and high GS were associated with poorer OS and PCSS. No factors were identified in M1-LV. The HR(OS) for HV with high BB selected for docetaxel plus TS+ENZA vs TS+ENZA alone was 1.28 (95%CI 0.76-2.17).ConclusionsHigh ALP, as a possible indicator of BB in pts without visceral mets, was prognostic in HV mHSPC for PSA-PFS, PCSS, and OS. High GS, but not T-stage, was associated with poorer outcomes in HV. Stratification of highest risk mHSPC may help define cohorts for further therapy intensification. Table: 1618P Univariable analysis of OS M1-HV, N=439 N HR (95% CI) p-val 5-year OS (%) Bone burden (high / low) 179 / 165 1.64 (1.23-2.2) <0.001 43 v 59 Gleason (8-10 / <8) 279 / 58 1.80 (1.14-2.83) 0.012 52 v 72 Visceral met (y / n) 95 / 344 1.0 (0.74-1.36) 1.0 54 v 50 T-stage (T3-4 / T1-2) 210 / 93 1.2 (0.86-1.69) 0.29 52 v 61 M0-HV, N=163 Bone burden (high / low) 41 / 77 2.17 (1.32-3.55) 0.002 37 v 58 Gleason (8-10 / <8) 79 / 68 1.61 (0.99-2.62) 0.056 49 v 66 T-stage (T3-4 / T1-2) 69 / 55 1.40 (0.81-2.40) 0.227 55 v 62 Clinical trial identificationNCT02446405.Legal entity responsible for the studyThe Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP).FundingThis study was conducted by the Australian and New Zealand Urogenital and Prostate Trials Group Ltd. (ANZUP) in collaboration with the NHMRC Clinical Trials Centre, University of Sydney. This ANZUP investigator-initiated study was financially supported by Astellas. ANZUP was supported by theAustralian Government through a Cancer Australia infrastructure Grant. The NHMRC CTC was supported by an NHMRC Program Grant. This study was conducted by the Australian and New Zealand Urogenital and Prostate Trials Group Ltd. (ANZUP) in collaboration with the NHMRC Clinical Trials Centre, University of Sydney. This ANZUP investigator-initiated study was financially supported by Astellas. ANZUP was supported by theAustralian Government through a Cancer Australia infrastructure Grant. The NHMRC CTC was supported by an NHMRC Program Grant. This ANZUP investigator-initiated study was financially supported by Astellas. ANZUP was supported by theAustralian Government through a Cancer Australia infrastructure Grant. The NHMRC CTC was supported by an NHMRC Program Grant.DisclosureA.A. Hamid: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, MSD; Financial Interests, Personal, Invited Speaker: Bayer; Non-Financial Interests, Institutional, Local PI: Astellas. 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, Institutional, Invited Speaker, Bayer paid for travel to Lisbon APEX meeting and accommodation. I gave 3 talks and honorarium paid to be institution: 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, Full or part-time Employment, I am a medical oncologist, Director of Research and Chief Clinical Officer of this cancer centre: Chris O'Brien Lifehouse; Financial Interests, Personal, Full or part-time Employment, I am a member of the Garvan Faculty and Laboratory Head: Garvan Institute of Medical Research; Financial Interests, Personal, Stocks/Shares, Stock options: Imagion Biosystems; Financial Interests, Personal, Stocks/Shares: My Emergency Doctor; Financial Interests, Institutional, Other, I am inventor of a patent lead by my institution above: International (PCT) Patent Application No. PCT/AU2023/050849Prognostic Markers (plasma lipid prognostic signature in metastatic prostate cancer).Inventors: Horvath L, Meikle P, Scheinberg S, Lin HM, Sullivan D: Chris O'Brien Lifehouse; 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, ENZAMET, ENZA-P, Upfront PSMA, ANZAdapt, GUIDE: ANZUP; Financial Interests, Institutional, Local PI, HP-518-CS-001: Hinova; Financial Interests, Institutional, Local PI, JANX007: Janux Therapeutics; Non-Financial Interests, Leadership Role, Professor of Medical Oncology (Genitourinary cancer): University of Sydney; Non-Financial Interests, Leadership Role, Adjunct Professor: University of New South Wales. R. Zielinski: Financial Interests, Personal, Advisory Board: MSD, JANSSEN; Financial Interests, Institutional, Research Funding: ROCHE, AstraZeneca. 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.: Bristol Myer Squib; 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 Bristol Myer Squibb sponsored studies and don't receive any renumeration for this.: Bristol Myer Squibb; 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 Priincipal 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 Bristol Myer Squibb sponsored trial and I do not receive renumeration for this.: Bristol Myer Squibb. M.N. Reaume: Financial Interests, Personal, Advisory Board: Ipsen, Pfizer, EMD Serono, Novartis. D.W. 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. R.S. McDermott: Financial Interests, Personal, Advisory Board: Pfizer, Amgen, BMS, Bayer, Janssen, Clovis; Financial Interests, Personal, Invited Speaker: MSD, Ipsen, Astellas; Financial Interests, Personal, Invited Speaker, Speaker at Ad board: Merck Serono; Financial Interests, Institutional, Coordinating PI: MSD; Financial Interests, Institutional, Local PI: Clovis, BMS, Regeneron, Bayer, Astellas; Financial Interests, Institutional, Local PI, Clinical Trial: Seagen. K.N. Chi: Financial Interests, Personal, Other, Honoraria: Astellas, AstraZeneca, BMS, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche. 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; Financial Interests, Institutional, Research Grant, Illuminate, Phaedra: AstraZeneca. 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, Institutional, Local PI, Institutional support for clinical research: Movember Foundation, Merck/MSD, Bristol Myers Squibb, Exelixis, Astellas, Pfizer, AstraZeneca, Roche / Genentech, Eisai, Bayer, Janssen, Ipsen, Seagen; Financial Interests, Institutional, Local PI, EPI-7386-CS-010 trial: ESSA Pharma; Non-Financial Interests, Member of Board of Directors, Director and Chair; unremunerated: 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, Xennials Therapeutics, Telix Therapeutics, AstraZeneca, Bayer; 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. C. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Genentech Roche, Bayer, Astellas, Pfizer, Pfizer, Sanofi, Lilly; Financial Interests, Personal, Other, Consultancy: Janssen, MSD; Financial Interests, Personal, Advisory Board: Point, Cellcentric; Financial Interests, Personal, Advisory Board, Consultant: Advancell; Financial Interests, Personal, Advisory Board, Advisory Boards: BMS; Financial Interests, Personal, Advisory Board, Consutlant: Amphista; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Personal, Stocks/Shares, Consultant: Advancell; Financial Interests, Institutional, Advisory Board, Abiraterone plus cabozantinib: Exelixis; Financial Interests, Institutional, Research Grant: Bayer, Janssen, Astellas, Pfizer, Dendreon, Sanofi. All other authors have declared no conflicts of interest.