173P - Clinical outcomes in stratification subgroups in the ARASENS study in metastatic hormone-sensitive prostate cancer (mHSPC)

Background

In ARASENS (NCT02799602), darolutamide (DARO) + androgen-deprivation therapy (ADT) + docetaxel significantly reduced risk of death by 32.5% (HR 0.68, 95% CI 0.57–0.80; P<0.001) vs placebo (PBO) + ADT + docetaxel in patients (pts) with mHSPC. We investigated clinical outcomes in prespecified stratification subgroups based on extent of disease and alkaline phosphatase (ALP), both known prognostic factors.

Methods

Pts with mHSPC were randomized 1:1 to DARO 600 mg or PBO twice daily + ADT + docetaxel, stratified by metastatic spread (TNM classification: nonregional lymph node metastases only [M1a]; bone ± lymph node metastases [M1b]; visceral ± lymph node/bone metastases [M1c]) and ALP (< or ≥ upper limit of normal [ULN]). The primary endpoint was overall survival (OS). Key secondary endpoints were times to castration-resistant prostate cancer (CRPC), pain progression, first symptomatic skeletal event (SSE), and subsequent life-prolonging antineoplastic therapy, and safety.

Results

were based on 1305 (DARO, 651; PBO, 654) randomized pts. 3% of pts had M1a (not analyzed further), 79.5% had M1b, and 17.5% had M1c disease; 55.5% had ALP ≥ULN. All stratification subgroups showed OS benefits of DARO vs PBO, with stratified HRs (95% CIs) of 0.66 (0.54–0.80) for M1b and 0.76 (0.53–1.10) for M1c; 0.65 (0.47–0.89) for ALP

Conclusions

In pts with mHSPC, DARO + ADT + docetaxel consistently improved OS and key patient-relevant secondary endpoints vs ADT + docetaxel in stratification subgroups based on extent of disease and ALP. AE rates were similar in both arms. Table: 173P

Secondary endpoints by stratification subgroup: DARO vs PBO

Clinical trial identification

Editorial acknowledgement

Open Health Group 20 Old Bailey, London, EC4M 7AN, United Kingdom.

Legal entity responsible for the study

The authors.

Funding

Bayer Healthcare Pharmaceuticals.

Disclosure

B. Tombal: Financial Interests, Personal, Advisory Board: Astellas, Bayer, Amgen, Janssen, Sanofi, Myovant, Novartis (AAA), Pfizer, MSD, AstraZeneca; Financial Interests, Personal, Invited Speaker: Astellas, Amgen, Ferring; Financial Interests, Personal, Expert Testimony: Astellas; Non-Financial Interests, Personal, Invited Speaker, Past President: European Organisation of Research and Treatment of Cancer (EORTC); Non-Financial Interests, Personal, Invited Speaker, Education in the field of Oncology: ISSECAM. F. Saad: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Sanofi, Pfizer, Myovant, Novartis; Financial Interests, Institutional, Invited Speaker: Novartis, Astellas, Bayer, Janssen, Sanofi, BMS, Amgen, Pfizer. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Personal, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Personal, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Personal, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Personal, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Personal, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Personal, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. E. D. Crawford: Non-Financial Interests, Personal, Invited Speaker: UC San Diego School of Medicine. H. Joensuu: Financial Interests, Personal, Advisory Board, Senior consultant: Orion Pharma; Financial Interests, Personal, Advisory Board, Chair of the Scientific Advisory Board: Neutron Therapeutics, Maud Kuistila Foundation; Financial Interests, Personal, Invited Speaker: Deciphera Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment, Until Aug. 31, 2020: Orion Pharma; Financial Interests, Personal, Stocks/Shares: Orion Pharma, Sartar Therapeutics. All other authors have declared no conflicts of interest.