Dr. Tombal on Darolutamide Monotherapy in Newly Diagnosed mHSPC

Bertrand Tombal, MD, PhD, professor of physiology, chair of the Division of Urology, the Université catholique de Louvain, the Cliniques universitaires Saint-Luc, in Brussels, Belgium, discusses the rationale for conducting a phase 2 study (NCT02972060) of darolutamide (Nubeqa) monotherapy in newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC).

The open-label EORTC-GUCG 1532 study was designed to investigate the efficacy of darolutamide, as well as the treatment’s ability to achieve prostate-specific antigen (PSA) suppression and lower testosterone in the absence of androgen-deprivation therapy (ADT) for patients with hormone-naïve, histologically confirmed prostate cancer. Patients across all stages were enrolled in the trial and were required to have a maximum of 4 metastatic lesions, be eligible for hormonal treatment, have an ECOG performance status of 0, and a life expectancy greater than 1 year, Tombal says. The primary end point of the trial was the proportion of patients achieving PSA response at 6 months relative to baseline. Moreover, PSA response was defined as PSA decline greater than 80%, Tombal explains.

Results showed that darolutamide monotherapy was associated with a significant PSA response in this patient population, Tombal continues. At week 24, the PSA response rate was 100% in the monotherapy arm, with a median range decrease of 99.6%. Moreover, this response was comparable with responses with darolutamide plus ADT, Tombal details. Serum testosterone levels in the darolutamide monotherapy arm also increased by a median range of 43.4%. In terms of safety data, 45.2% of patients reported primarily grade 1/2 treatment-related adverse events (TRAEs).

Additional quality-of-life (QoL) data was assessed using the standard EORTC QLQ-PR25 questionnaire, as well as the Aging Male Symptoms scale for male hypergonadism, Tombal adds. Darolutamide alone elicited a lower mean change score according to the EORTC and a lower AMS questionnaire score. This indicates that the regimen elicits lesser less severe hypogonadism-related AEs, respectively. 

Editor’s Note: Dr. Tombal reports serving as a consultant or in an advisory role for Astellas Pharma, Bayer, Ferring, Janssen, Myovant Sciences, Pfizer, Sanofi, Steba Biotech, Takeda; he reports institutional research funding from Ferring; he has served on the Speakers' Bureau for Amgen, Astellas Pharma, Janssen; he received honoraria from Amgen, Astellas Pharma, Bayer, Ferring, Janssen, Myovant Sciences, Pfizer, Sanofi.