Abstract 630P
Background
Men with nonmetastatic castration-resistant prostate cancer (nmCRPC) are generally asymptomatic and may receive prolonged treatment with androgen receptor inhibitors (ARIs). Understanding the burden and time course of adverse events (AEs) commonly associated with ARIs that may impact patients’ daily life will help inform optimal treatment selection for men with nmCRPC. We present analyses of time to AEs of interest associated with some ARIs (fatigue, falls, fracture, hypertension, mental impairment, and rash) and the cumulative incidence of these AEs, grade 3/4 AEs, and serious AEs from ARAMIS.
Methods
Men with nmCRPC were randomized 2:1 to darolutamide (DARO; n=955) or placebo (PBO; n=554) while continuing androgen deprivation therapy. The cumulative incidence of AEs was analyzed using Kaplan-Meier estimates for the first 24 months of the double-blind (DB) period to ensure >10% of the population in each treatment cohort. Time interval–specific analysis determined new event rates at each scheduled study visit.
Results
During the first 24 months of the DB period, the incidence of AEs of interest in the DARO group was low and ≤2% different from that in the PBO group, except for fatigue. During the first month of DARO and PBO treatment, new event rates were very low and similar for falls (0.2%, 0.7%), fractures (0.4%, 0.5%), mental impairment (0%, 0.4%), hypertension (1.7%, 1.1%), and rash (0.7%, 0.2%). In men who had fatigue during the first 24 months (DARO, 12.6% and PBO, 8.3%), almost half of the men experienced fatigue onset during the first month in both arms (DARO, 5.9% vs PBO, 4.0%). The cumulative incidence of rash was 2.9% (PBO 1.1%) at 24 months, with half of the events occurring in the first 4 months and almost all being grade 1 or 2. The rate of initial onset and cumulative incidence of grade 3/4 AEs and serious AEs were similar for DARO and PBO groups over 24 months.
Conclusions
The time course profile of most AEs of interest, grade 3/4 AEs, and serious AEs confirms the safety profile of DARO, showing a similar onset and cumulative incidence versus PBO. Most events of fatigue were reported early in treatment, and the incidence of rash was very low, with almost all being grade 1 or 2 events.
Clinical trial identification
NCT02200614.
Editorial acknowledgement
Medical writing support was provided by Michelle McDermott, PharmD, Open Health Medical Communications (London, UK), supported by Bayer.
Legal entity responsible for the study
Bayer AG and Orion Pharma.
Funding
Bayer AG and Orion Pharma.
Disclosure
C.J. Gratzke: Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: GSK; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: Lillyl; Financial Interests, Personal, Other, Honoraria: Recordati; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Rottapharm; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Meditate; Financial Interests, Personal, Other, Honoraria: STEBA Biotech; Financial Interests, Personal, Other, Honoraria: Olympus; Financial Interests, Personal, Other, Honoraria: Procept; Financial Interests, Personal, Research Grant: Astellas; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: GSK; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Recordati. K. Fizazi: Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Orion Pharma; Financial Interests, Personal, Advisory Role: Curevac; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: ESSA; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Janssen; Financial Interests, Personal, Other, Travel, accommodation, expenses: MSD; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Bayer. N.D. Shore: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Janssen Scientific Affairs; Financial Interests, Personal, Advisory Role: Dendreon; Financial Interests, Personal, Advisory Role: Tolmar; Financial Interests, Personal, Advisory Role: Ferring; Financial Interests, Personal, Advisory Role: Medivation/Astellas; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Genetech/Roche; Financial Interests, Personal, Advisory Role: Myovant Sciences; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Dendren. M.R. Smith: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Astellas Pharma. M. Grabbert: Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, Travel accommodation, expenses: Astellas; Financial Interests, Personal, Other, Travel accommodation, expenses: MSD; Financial Interests, Personal, Other, Travel accommodation, expenses: Janssen; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: Medac; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Janssen. J. Carles: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Astellas Pharma; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Johnson & Johnson; Financial Interests, Personal, Other, Travel, accommodation, expenses: BMS; Financial Interests, Personal, Other, Travel, accommodation, expenses: Ipsen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche; Financial Interests, Personal, Other, Travel, accommodation, expenses: AstraZeneca; Financial Interests, Institutional, Research Grant: AB Science; Financial Interests, Institutional, Research Grant: Aragon Pharmaceuticals; Financial Interests, Institutional, Research Grant: Arog Pharmaceuticals; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Aveo Pharmaceuticals; Financial Interests, Institutional, Research Grant: Bayer AG; Financial Interests, Institutional, Research Grant: Blueprint Medicines Corporation; Financial Interests, Institutional, Research Grant: BN Immunotherapeutics; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim España; Financial Interests, Institutional, Research Grant: Sanofi Aventis; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Clovis Oncology; Financial Interests, Institutional, Research Grant: Cougar Biotechnology; Financial Interests, Institutional, Research Grant: Deciphera Pharmaceuticals; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: F. Hoffmann-La Roche; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Incyte Corporation; Financial Interests, Institutional, Research Grant: Janssen-Cilag; Financial Interests, Institutional, Research Grant: Karyopharm Therapeutics; Financial Interests, Institutional, Research Grant: Laboratoires Leurquin Mediolanum; Financial Interests, Institutional, Research Grant: SAS; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Medimmune; Financial Interests, Institutional, Research Grant: Millennium Pharmaceuticals; Financial Interests, Institutional, Research Grant: Nanobiotix SA; Financial Interests, Institutional, Research Grant: Novartis Farmacéutica SA; Financial Interests, Institutional, Research Grant: Pfizer SLU; Financial Interests, Institutional, Research Grant: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Sanofi-Aventis SA; Financial Interests, Institutional, Research Grant: SFJ Pharma II; Financial Interests, Institutional, Research Grant: Teva Pharma SLU. T. Lebret: Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Astellas; Financial Interests, Personal, Other, Honoraria: Janssen. E. Vjaters: Financial Interests, Personal, Research Grant: Orion Pharma; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Ipsen; Financial Interests, Personal, Research Grant: Janssen. M. Miskic: Financial Interests, Personal, Full or part-time Employment: Bayer. A. Schmall: Financial Interests, Personal, Full or part-time Employment: Bayer. M.A. Le Berre: Financial Interests, Personal, Full or part-time Employment: Bayer. F. Verholen: Financial Interests, Personal, Full or part-time Employment: Bayer. All other authors have declared no conflicts of interest.