Multinational prospective study of darolutamide with concomitant lipid-modifying agents in nmCRPC: interim analysis of DAROL

Darolutamide in combination with androgen deprivation therapy (ADT) is approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC). Many patients with nmCRPC receive concomitant lipid-modifying agents (LMAs). The ongoing multinational, prospective DAROL study assesses clinical practice outcomes of darolutamide plus ADT in nmCRPC. A planned interim analysis of DAROL assessing safety and efficacy of darolutamide with or without concomitant LMAs. The interim analysis took place after 799 patients had received at least 12 months of darolutamide. At baseline, 258 of 799 patients (32.3%) were receiving at least 1 LMA, most frequently atorvastatin (n=110). The incidence of treatment-emergent adverse events (TEAEs) was higher in the any LMA versus no LMA subgroup (74.4% versus 54.5%) and in the rosuvastatin versus no rosuvastatin subgroup, but similar in the any LMA versus cardiac disease without LMA use subgroup (with no grade 5 treatment-related events). Discontinuation of darolutamide due to TEAEs was low in the any LMA (7.0%) and rosuvastatin (3.6%) subgroups. Darolutamide maintained effectiveness in combination with LMAs, with no difference in overall survival between the any LMA and no LMA subgroups or between the any LMA and cardiac disease without LMA use subgroups. Time to PSA progression was also similar between the subgroups, whereas metastasis-free survival favored the no LMA subgroup. The authors conclude that the interim analysis supports darolutamide as a standard-of-care treatment option for nmCRPC, including those receiving concomitant LMAs.