1784P - Prostate-specific antigen (PSA) outcomes with darolutamide (DARO): Androgen-deprivation therapy (ADT) and docetaxel (DOC) in patients (pts) with high- and low-volume metastatic hormone-sensitive prostate cancer (mHSPC) in ARASENS

Background

In ARASENS (NCT02799602), DARO + ADT + DOC significantly reduced risk of death by 32.5% (HR 0.68; 95% CI 0.57–0.80; P<0.0001) vs ADT + DOC in pts with mHSPC. In post hoc analyses, HRs for overall survival (OS) were similar for pts with high-volume (HV HR 0.69; 95%CI 0.57–0.82) and low-volume (LV HR 0.68; 95% CI 0.41–1.13) disease. We report PSA outcomes in these pt subgroups.

Methods

Pts with mHSPC were randomized to DARO 600 mg twice daily or placebo (PBO), both with ADT + DOC. PSA was measured at screening and every 12 weeks. Analyses included the proportion of patients achieving undetectable PSA (<0.2 ng/mL) and time to PSA progression. The association between undetectable PSA at any time with time to PSA progression and OS was evaluated using Kaplan-Meier estimates with HRs (95% CI) based on a stratified Cox regression model.

Results

Of 1305 pts, 1005 (77%) had HV disease and 300 (23%) had LV disease. Rapid undetectable PSA response as early as 12 weeks was achieved in nearly twice as many patients receiving DARO vs PBO and continued to increase for both HV and LV subgroups over time (at 24 weeks: HV 43.1% vs 21.7%, LV 66.9% vs 31.5%; at 52 weeks, HV 54.7% vs 23.6%, LV 77.9% vs 34.9%; and at any time, HV 62.2% vs 25.8%, LV 83.8% vs 38.4%). Time to PSA progression was prolonged in pts receiving DARO vs PBO in HV (HR 0.30; 95% CI 0.24–0.37) and LV (HR 0.09; 95% CI 0.05–0.18) pts (4-yr PSA progression-free rates: HV 65.8% vs 27.0%; LV 91.7% vs 36.3%). Pts receiving DARO who achieved undetectable PSA had improved time to PSA progression (HV HR 0.11, 95% CI 0.07–0.16; LV HR 0.02, 95% CI 0.004–0.10) and improved OS (HV HR 0.20; 95% CI 0.15–0.27; LV HR 0.34; 95% CI 0.14–0.79) vs those who did not.

Conclusions

Early treatment intensification with DARO + ADT + DOC allows pts with HV and LV mHSPC to achieve rapid, deep, and durable PSA responses that are associated with improved time to PSA progression and OS.

Clinical trial identification

NCT02799602.

Editorial acknowledgement

Medical writing support was provided by Michelle McDermott, of OPEN Health Communications (London, UK).

Legal entity responsible for the study

Bayer AG and Orion Pharma.

Funding

Bayer AG and Orion Pharma.

Disclosure

F. Saad: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Sanofi, Pfizer, Myovant, Novartis, AstraZeneca, Merck, Myovant; Financial Interests, Institutional, Local PI: Novartis, Astellas, Bayer, Janssen, Sanofi, BMS, Amgen, Pfizer, Merck; Financial Interests, Institutional, Coordinating PI: AstraZeneca. M. Hussain: Financial Interests, Personal, Other, Honoraria: UroToday, Merck, Astellas Pharma, AstraZeneca, Precisca, Medscape Zero, Targeted Oncology, Great Debates and Updates in GU Oncology, Clinical Care Options; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Merck, Janssen, Tempus, Bayer, AstraZeneca, GSK, Convergent Therapeutics; Financial Interests, Institutional, Research Funding: Genentech, Pfizer, PCCTC, AstraZeneca, Bayer, Arvinas; Financial Interests, Personal, Licensing Fees or royalty for IP: Systems and methods for tissue imaging, method of treating cancer. B. Tombal: Financial Interests, Personal, Advisory Board: Astellas, Bayer, Amgen, Janssen, Sanofi, Myovant, Novartis (AAA), Pfizer, Astellas, MSD, AstraZeneca; Financial Interests, Personal, Invited Speaker: Astellas, Amgen, Ferring; Non-Financial Interests, Member of Board of Directors, Past President: European Organisation of Research and Treatment of Cancer (EORTC); Non-Financial Interests, Member of Board of Directors, Education in the field of Oncology: ISSECAM. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Personal, Advisory Board, February 2022: Arvinas; Financial Interests, Personal, Advisory Board, April 2022: Macrogenics; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the CAPITELLO 281 phase 3 trial: AstraZeneca; Non-Financial Interests, Principal Investigator, Chair of the TALAPRO-2 and TALAPRO-3 phase 3 trials: Pfizer; Non-Financial Interests, Principal Investigator, Chair of the RADIANT phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the TRITON-3 phase 3 trial: Clovis. C.N. Sternberg: Financial Interests, Personal, Advisory Board, AD board and speaker at ESMO: Pfizer; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Astellas, Sanofi-Genzyme, Roche-Genentech, Foundation Medicine, Immunomedics, Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board, Was the head if the oversignt committee, of Phase III trial but last meeting over 1 year ago: Seattle Genetics; Financial Interests, Personal, Other, AD board: BMS; Financial Interests, Personal, Other, Speaker, owned by Prostate Cancer Foundation: Uro Today; Financial Interests, Personal, Other, Speaker, CME activities: Medscape. E.D. Crawford: Financial Interests, Personal, Full or part-time Employment: Blue Earth Diagnostics; Financial Interests, Personal, Leadership Role: Blue Earth Diagnostics; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Advisory Role: Bayer, Tolmar, Pfizer/Astellas, MDxHealth, Janssen Oncology; Financial Interests, Personal, Speaker’s Bureau: Bayer. M. Boegemann: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Other, Honoraria: Janssen Cilag, Astellas Pharma, Bayer/Vital, Sanofi/Aventis, MSD, BMS, Pfizer, Novartis, Ipsen, EUSA Pharma, Merck, Eisai, Amgen, AstraZeneca, Roche, Advanced Accelerator Applications; Financial Interests, Personal, Advisory Role: Bayer, Janssen Cilag, Astellas Pharma, AstraZeneca, MSD, BMS, Ipsen, Roche, Novartis, Merck, Sanofi, Eisai; Financial Interests, Institutional, Research Funding: Janssen Cilag, Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen Cilag, Bayer, Amgen, BMS GmbH & Co KG. R. Tutrone: Financial Interests, Personal, Advisory Role: Astellas, Bayer, Novartis, Point Biopharma, Pfizer, Myovant, Nymox, Merck, Veru. N. Littleton, S. Srinivasan, F. Verholen, I. Kuss: Financial Interests, Personal, Full or part-time Employment: Bayer. M.R. Smith: Financial Interests, Personal, Advisory Role: Bayer, Janssen Oncology, Amgen, Pfizer, Lilly, Novartis, Astellas Pharma; Financial Interests, Institutional, Research Funding: Janssen Oncology, Bayer, Lilly, ESSA, ORIC Pharmaceuticals.