Darolutamide is an androgen receptor inhibitor that increases overall survival in combination with androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer (PCa). This phase 2 study assessed the efficacy and safety of darolutamide as monotherapy without ADT in patients with eugonadal testosterone levels.
This was a 24-wk, open-label, randomized study of patients with hormone-sensitive, histologically confirmed PCa requiring gonadotropin-releasing hormone (GnRH); an Eastern Cooperative Oncology Group performance status score of 0/1; and life expectancy >1 yr. All patients received darolutamide 600 mg bid or a commercially available GnRH analog. The primary endpoint is a prostate-specific antigen (PSA) response, defined as a ≥80% decline at week 24 relative to baseline in the darolutamide study arm. The GnRH arm is used as an internal control. The secondary endpoints included changes in T levels, safety/tolerability, and quality of life.
Among 61 men enrolled, the median (range) age was 72 yr (53-86 yr); 42.6% of them had metastases. In the darolutamide arm, the evaluable population with available PSA values at baseline and week 24 consisted of 23 patients. Twenty-three (100%) evaluable darolutamide patients achieved a PSA decline of >80% at week 24 (primary endpoint), with a median (range) decrease of -99.1% (-91.9%, -100%). Serum T levels increased by a median (range) of 44.3 (5.7-144.0) at week 24, compared with baseline. In the darolutamide arm, 48.4% of men reported drug-related adverse events (AEs; mostly grade 1 or 2). The most frequent treatment-emergent AEs included gynecomastia (35.5%), fatigue (12.9%), hot flush (12.9%), and hypertension (12.9%). Health-related quality of life measures are descriptive, and GnRH arm results will be presented as an internal reference.
Darolutamide monotherapy was associated with a significant PSA response in nearly all men with hormone-naïve PCa. Testosterone-level changes and most common AEs (gynecomastia, fatigue, hypertension, and hot flush) were consistent with potent androgen receptor inhibition.
In this study, we report the first use of darolutamide, a novel antiandrogen, as monotherapy without androgen deprivation therapy (ADT). The study shows that darolutamide induce a profound suppression of prostate-specific antigen in all patients, with a safety profile different from that of ADT.
European urology oncology. 2024 Jan 24 [Epub ahead of print]
Bertrand F Tombal, Francisco Gomez-Veiga, Alvaro Gomez-Ferrer, Fernando López-Campos, Piet Ost, Thierry Andre Roumeguere, Bernardo Herrera-Imbroda, Lionel A D'Hondt, Magali Quivrin, Paolo Gontero, Salvador Villà, Hussein Khaled, Beatrice Fournier, Jammbe Musoro, Joanna Krzystyniak, Yassin Pretzenbacher, Yohann Loriot
Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium. Electronic address: ., Complexo Hospitalario Universitario de A Coruña, Coruña, Spain., IVO, Valencia, Spain., Hospital Universitario Ramón y Cajal, Madrid, Spain., Ghent University Hospital, Ghent, Belgium., Department of Urology, Hôpital Universitaire de Bruxelles Erasme Hospital, ULB, Anderlecht, Belgium., Hospital Universitario Virgen De La Victoria, Malaga, Spain., CHU UCL NAMUR site Godinne, Yvoir, Belgium., Radiation Oncology Department, Anticancer Center, Centre Georges Francois Leclerc, Dijon, France., Dipartimento di Discipline Medico Chirurgiche, Clinica Urologica, University of Torino, Torino, Italy., Radiation Oncology, Department of Oncology, Badalona, Barcelona, Catalonia, Spain., National Cancer Institute, Cairo, Egypt., EORTC, Brussels, Belgium., Département de Médecine Oncologique, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France.