In patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable safety/tolerability profile. This post hoc analysis of ARAMIS evaluated efficacy and safety in patients by number of comorbidities and concomitant medications.
Patients with nmCRPC were randomised 2:1 to darolutamide (n = 955) or placebo (n = 554) while continuing androgen-deprivation therapy. Overall survival (OS) and treatment-emergent adverse events (TEAEs) were evaluated in subgroups by median numbers of ongoing comorbidities and concomitant medications. HRs were determined from univariate analysis using Cox regression.
Median numbers of comorbidities and concomitant medications were 6 and 10, respectively, with 41.6% of patients having >6 comorbidities and 48.8% taking >10 concomitant medications. For patients with ≤ 6 and >6 comorbidities, darolutamide increased OS versus placebo (hazard ratio [HR] 0.65 and 0.73, respectively), and this benefit was consistent for cardiovascular, metabolic, and other comorbidities (HR range: 0.39-0.88). For patients taking ≤ 10 and >10 concomitant medications, increased OS was also observed with darolutamide versus placebo (HR 0.76 and 0.66, respectively), and the benefit was consistent across medication classes (HR range: 0.45-0.80). Incidences of TEAEs and TEAEs leading to treatment discontinuation with darolutamide were similar to placebo across subgroups by numbers of comorbidities and concomitant medications.
The OS benefit and safety of darolutamide remained consistent with that observed in the overall ARAMIS population, even in patients with high numbers of comorbidities or concomitant medications.
NCT02200614.
Darolutamide increased overall survival versus placebo, and incidences of most adverse events were similar between treatments in patients with ≤ 6 or >6 comorbidities and those taking ≤ 10 or >10 concomitant medications.
European journal of cancer (Oxford, England : 1990). 2023 Jul 27 [Epub ahead of print]
Karim Fizazi, Neal D Shore, Matthew Smith, Rodrigo Ramos, Robert Jones, Günter Niegisch, Egils Vjaters, Yuan Wang, Shankar Srinivasan, Toni Sarapohja, Frank Verholen
Institut Gustave Roussy, University of Paris Saclay, Villejuif, France. Electronic address: ., Carolina Urologic Research Center/Genesis Care, Myrtle Beach, South Carolina, USA., Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts, USA., Departamento de Cirurgia, Instituto Português de Oncologia, Lisboa, Portugal., University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK., Department of Urology, University Hospital and Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Urological Center, P. Stradins Clinical University Hospital, Riga, Latvia., Global Medical Affairs, Oncology, Bayer Healthcare, Whippany, New Jersey, USA., Clinical Operations and Data Science, Orion Corporation, Espoo, Finland., Global Medical Affairs, Oncology, Bayer Consumer Care AG, Basel, Switzerland.