1360MO - Quality of life and patient-relevant endpoints with darolutamide in the phase III ARASENS study

Background

In ARASENS, darolutamide (DARO) + androgen-deprivation therapy (ADT) + docetaxel significantly reduced risk of death by 32.5% vs placebo (PBO) + ADT + docetaxel (HR 0.68, 95% CI 0.57–0.80) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). Given the potentially long treatment duration, the impact of DARO + ADT + docetaxel on pt-relevant endpoints is important to assess.

Methods

Pts were randomized 1:1 to DARO 600 mg twice daily or PBO + ADT + docetaxel. Pt-relevant endpoints were all-cause and prostate cancer related death; time course of adverse events (AEs) of special interest; and quality of life (QoL) based on time to worsening (TTW) of disease-related physical symptoms.

Results

In the safety analysis set (n=1302), the DARO + ADT + docetaxel arm (n=652) had fewer all-cause deaths (35.1% vs 46.8%) and prostate cancer related deaths (26.1% vs 36.0%) vs the PBO + ADT + docetaxel arm (n=650). Despite longer treatment exposure with DARO vs PBO (median 41.0 vs 16.7 months), overall AE incidence was similar in the 2 arms. Fatigue (DARO 33.1%, PBO 32.9%) and rash (16.6%, 13.5%) appeared predominantly in treatment months 1–3 and incidence decreased rapidly thereafter. Cumulative incidences of falls, fractures, and mental impairment were low (<10%) and similar between arms. The incidence of cardiac disorders was constant over time and similar between arms (DARO 10.9%, PBO 11.7%). Incidence of hypertension was 13.7% vs 9.2%, with similar distribution over time. Most pts had high baseline QoL scores that were maintained over time, with comparable TTW in both arms. Table: 1360MO

Conclusions

Early treatment intensification with DARO + ADT + docetaxel improved pt-relevant endpoints, with reduced all-cause and prostate cancer related deaths and similar incidences and time course for most AEs of special interest vs PBO + ADT + docetaxel, notably with no increase in cardiac disorders. QoL was maintained over time, and DARO had no adverse impact on QoL, including in pts with poor prognosis.

Clinical trial identification

NCT02799602.

Editorial acknowledgement

Editorial assistance in the preparation of this abstract was provided by Sara Black of OPEN Health Communications, London, UK, with financial support from Bayer.

Legal entity responsible for the study

Bayer HealthCare.

Funding

Bayer HealthCare.

Disclosure

K. Fizazi: Financial Interests, Institutional, Funding, Consulting fees, Speakers Bureau, Ad Board: Amgen, Astellas, AstraZeneca, Bayer, Novartis, Sanofi, Janssen; Financial Interests, Personal, Other: Orion, Curvec; Financial Interests, Institutional, Funding: Lilly. M.R. Smith: Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Other, Consulting fees: Amgen, Bayer, Janssen, Lilly, Pfizer. M. Hussain: Financial Interests, Institutional, Funding: Bayer, Genentech, AstraZeneca; Financial Interests, Institutional, Advisory Board: Pfizer, Novartis, AstraZeneca/Merck, Janssen, Arvinas. F. Saad: Financial Interests, Institutional, Funding: Bayer, AstraZeneca, Astellas, Janssen, Merck, Novartis, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Bayer, AstraZeneca, Astellas, Janssen, Merck, Novartis, Pfizer; Non-Financial Interests, Other: Bayer, AstraZeneca, Astellas, Janssen, Merck, Novartis, Pfizer. C. Sternberg: Financial Interests, Institutional, Advisory Board: Bayer, MSD, Pfizer, Roche, AstraZeneca, Merck, Medscape, Astellas, Genzyme, Gilead, UroToday, Foundation Medicine, BMS, Impact Therapeutics. E.D. Crawford: Financial Interests, Institutional, Advisory Board: Janssen, Bayer, MDx, Tolmar; Financial Interests, Institutional, Invited Speaker: Genomic Health; Financial Interests, Institutional, Funding: NIH, Univ of Colorado Cancer Center; Financial Interests, Institutional, Speaker’s Bureau: Pfizer, Astellas; Financial Interests, Personal, Ownership Interest: 3rd Bx; Financial Interests, Institutional, Leadership Role: Carden Jennings. J.B. Aragon-Ching: Financial Interests, Personal, Advisory Role: Bayer, Janssen Oncology, Exelixis, Merck, Pfizer/EMD Serono, Immunomedics, AZD, Pfizer/Myovant; Financial Interests, Personal, Invited Speaker: BMS, Pfizer/EMD Serono, Astellas/Seagen. S. Thiele: Financial Interests, Personal, Full or part-time Employment: Bayer AG. S. Kapur: Financial Interests, Personal, Full or part-time Employment: Bayer SEA. A.F. Mohamed: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare. S. Srinivasan: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare. R. Li: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare. I. Kuss: Financial Interests, Personal, Full or part-time Employment: Bayer AG. H. Joensuu: Financial Interests, Personal, Full or part-time Employment: Orion Corporation Orion Pharma; Financial Interests, Personal, Stocks/Shares: Orion Corporation Orion Pharma, Sartar Therapeutics; Financial Interests, Institutional, Speaker’s Bureau: Neutron Therapeutics, Deciphera Pharmaceuticals. B. Tombal: Financial Interests, Institutional, Funding: Bayer, Ferring; Financial Interests, Institutional, Advisory Board: Bayer, Astellas, Amgen, Ferring, Janssen, Myovant, Novartis, Sanofi.