Real world prospective evaluation of clinical outcomes in patients with non-metastatic castrate resistant prostate cancer treated with darolutamide

Background: The RECORD Study is a real world data, prospective evaluation of clinical outcomes in patients with nmCRPC treated with Darolutamide. This study will increase the understanding of treatment response and management and in particular informregarding use of next generation imaging in this setting. Method(s): Patient data from 9 UK centres was collected based on the recommendation of NICE for Darolutamide as an option for the treatment of non-metastatic castrate resistant prostate cancer (nmCRPC) from November 2020. Data cut-off was 15 September 2022. The study is ongoing. Result(s): 87 patients were analysed with a median age of 78 (range 61-92). Median pre-treatment PSA and PSA doubling time (PSAdT) were 13 (range 1.99-110.6) mg/L and 5.05 (range 0.6 -10) months. 42 patients (49.4%) had pre-treatment PSAdT of <6 months and 43 (50.6%) patients had PSAdT of >=6 months (2 patients had no pre-treatment PSAdT data). 6 patients (6.90%) had next generation imaging prior to initiation of Darolutamide. Median duration of treatment on Darolutamide was 17 months for patients with pre-treatment PSAdT <6 months but median duration had not been reached for patients with pre-treatment PSAdT >=6 months after 24 months of treatment, a significant difference p=0.018 (HR=0.385, 95% CI 0.17-0.88). 30 patients have come off treatment so far (34.5%);21 (70%) for disease progression, 5 (16%) for a medical cause unrelated to the drug (e.g. COVID infection, reduced performance status secondary to pre-existing Parkinson's), 3 (10%) for unacceptable toxicity (rash, Grade3 fatigue, muscle aches, memory issues), and 1 patient died (unrelated). Conclusion(s): In the RECORD study, predominantly the diagnosis of nmCRPC is based on conventional imaging. The majority of patients respond and tolerate Darolutamide well, comparable with the ARAMIS trial. There is a significant difference between time on Darolutamide for those with pre-treatment PSAdT of<6 months compared with>=6 months. Further long-term toxicity, MFS and OS data will continue to be collected prospectively within the study.

LBA4 Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men with high-risk non-metastatic (M0) prostate cancer (PCa): Combined analysis from two comparisons in the STAMPEDE platform protocol

Background: Patients (pts) with high-risk M0 PCa are treated with ADT and when indicated, local radiotherapy (RT). Intensifying hormone treatment with AAP, ENZ or apalutamide continuous to progression improves outcomes of metastatic PCa but its efficacy in M0 PCa starting ADT is unknown. Methods: STAMPEDE is a multi-arm, multi-stage trial that, as part of 2 separate comparisons randomised PCa pts with M0 node positive or high-risk node negative (>1 T3/4, PSA ≥40ng/ml, Gleason 8-10 or relapsing) 1:1 to ADT (control) vs ADT with AAP (1000mg AA + 5mg P od) or ADT vs ADT with AAP + ENZ (160mg od) for 2 years (y), unless RT was omitted when treatment could be to progression. The primary end-point was metastasis-free survival (MFS, time to death or distant metastases). The sub-group of pts who received ADT +/- AAP was partially reported with metastatic pts in 2017 so one-sided type 1 error rate was set to 1.25%. All analyses were pre-specified, pooled using meta-analyses methods and stratified as described previously. Data frozen 3rd August 2021. Results: 1974 M0 pts at 113 sites in UK & Switzerland were randomised, 914 (Nov 2011 to Jan 2014) to ADT +/- AAP & 1060 (Mar 2016 to Jul 2014) to ADT +/- AAP + ENZ. Groups were well balanced: median age 68 y, range 43-86;median PSA 34 ng/ml, range 0.4-2773;Gleason 8-10, 79%;node positive 39%;planned for RT 85%. Median months to stopping AAP, 23.7 (IQR: 17.6-24.1);AAP when given with ENZ, 20.7 (IQR: 4.4-24);ENZ, 23.2 (IQR: 6.3-24). 180 MFS events occurred in the research group and 306 in the control group. AAP-based therapy improved MFS (HR 0.53, 95% CI 0.44-0.64, P=2.9×10- 11) & survival (HR 0.60, 95% CI 0.48-0.73, P=9.3×10-7): 6-y MFS from 69% to 82%, 6-y survival from 77% to 86%. Treatment effect was consistent in major subgroups and between AAP & AAP + ENZ randomisation periods (MFS HR=0.54, 95% CI 0.43-0.68;HR=0.53, 95% CI 0.39-0.71 respectively;interaction HR = 1.02, 95% CI: 0.70-1.50, p=0.908). Conclusions: 2 y of AAP-based therapy significantly improves MFS & survival of high-risk M0 PCa starting ADT and should be considered a new standard of care. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Astellas, Janssen. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Astellas;Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Sapience;Financial Interests, Personal, Advisory Board: Orion;Financial Interests, Personal, Royalties: Janssen;Financial Interests, Institutional, Research Grant: Janssen;Financial Interests, Institutional, Research Grant: Astellas;Non-Financial Interests, Principal Investigator: Janssen;Non-Financial Interests, Advisory Role: Janssen;Non-Financial Interests, Advisory Role: AstraZeneca;Non-Financial Interests, Principal Investigator: Astellas. L.C. Brown: Financial Interests, Institutional, Research Grant, FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca. N. Clarke: Financial Interests, Personal, Invited Speaker: Astellas;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Ferring;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Ferring;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Inst tutional, Research Grant: AstraZeneca. W. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics;Financial Interests, Personal, Invited Speaker, Speaker fee: Janssen;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Personal, Invited Speaker, Speaker fee: Astellas;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. R. Jones: Financial Interests, Personal, Advisory Board, advisory board attendance: AstraZeneca;Financial Interests, Personal, Advisory Board, advisory board attendance: Astellas;Financial Interests, Personal, Invited Speaker, Honoraria for speaking: Astellas;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Clovis;Financial Interests, Personal, Advisory Board: Exelixis;Financial Interests, Personal, Advisory Board: Ipsen;Financial Interests, Personal, Invited Speaker: Ipsen;Financial Interests, Personal, Advisory Board: Bristol Myers Squipp;Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Invited Speaker: Merck Serono;Financial Interests, Personal, Advisory Board: Merck Sharpe Dome;Financial Interests, Personal, Invited Speaker: Merck Sharpe Dome;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Institutional, Other, IDMC membership: Roche;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Institutional, Other, IDMC member: Stab;Financial Interests, Personal, Advisory Board: Novartis / AAA;Financial Interests, Institutional, Invited Speaker: Janssen;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: Tail;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: BioXcel;Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb;Financial Interests, Institutional, Invited Speaker: Novartis / AAA;Financial Interests, Institutional, Invited Speaker: Roche;Financial Interests, Institutional, Invited Speaker: MSK. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Advisory Board, 2018: Roche;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag;Financial Interests, Institutional, Advisory Board, 2020: Roche;Financial Interests, Institutional, Advisory Board, 2018: AAA International;Financial Interests, Institutional, Advisory Board, 2018: Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory Board, 2019: Tolero Pharmaceuticals;Financial Interests, Institutional, Advisory Board, 2020: MSD Merck Sharp & Dohme;Financial Interests, Institutional, Advisory Board, 2020: Pfizer;Financial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Invited Speaker, 2021: DESO;Financial Interests, Institutional, Advisory Board, 2021: BMS;Financial Interests, Institutional, Advisory Board, 2021: AAA International;Financial Interests, Institutional, Advisory Board, 2021: Orion;F nancial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Institutional, Advisory Board, 2021: Bayer;Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, Other, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Personal, Invited Speaker, 2021: SAMO - IBCSG;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems;Non-Financial Interests, Advisory Role, 2019: Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. S. Chowdhury: Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Huma;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Novartis/AAA;Financial Interests, Personal, Advisory Board: Beigene;Financial Interests, Personal, Advisory Board: Remedy Bio;Financial Interests, Personal, Advisory Board: Athenex;Financial Interests, Personal, Advisory Board: Telix;Financial Interests, Personal, Advisory Board: Clovis Oncology;Financial Interests, Personal, Stocks/Shares: Curve Life;Financial Interests, Institutional, Research Grant: Clovis Oncology;Non-Financial Interests, Advisory Role, Non-compensated advice: NHS England;Non-Financial Interests, Advisory Role: NICE NHS England. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer:Sanofi;Other, support to attend meetings or advisory boards in the past: Astellas, Jaansen, Bayer. C. Parker: Financial Interests, Personal, Advisory Board, Education Steering Committee: Bayer;Financial Interests, Personal, Invited Speaker, Speaker at prostate cancer educational events: Janssen;Financial Interests, Personal, Advisory Board, Advisory board on apalutamide: Janssen;Financial Interests, Personal, Advisory Board, Advisory board: Clarity Pharmaceuticals;Financial Interests, Personal, Advisory Board, Advisory board on relugolix: Myovant;Financial Interests, Personal, Advisory Board, Advisory board: ITM Oncologics. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Janssen;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Novartis;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Pfizer;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Sanofi. M.K. Parmar: Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facili ate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Clovis;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Novartis;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.