Исследование показало, что даролутамид имеет более благоприятный профиль безопасности по сравнению с другими ингибиторами андрогенных рецепторов при раке простаты

Compared to other androgen receptor inhibitors (ARIs) for the treatment of prostate cancer, darolutamide may have a lower risk of incremental harm for some adverse events (AEs), according to research published in the European Journal of Cancer. Although there have been no published head-to-head randomized controlled trials that compare the safety and efficacy of the ARIs darolutamide, apalutamide, and enzalutamide in prostate cancer treatment, evidence suggests that there may be differences in the tolerability profiles of these drugs, study researchers noted. In this post hoc, exploratory study, researchers evaluated data from pivotal phase 3 trials that compared ARI therapy plus androgen-deprivation therapy (ADT) to ADT alone in the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) or metastatic hormone-sensitive prostate cancer (mHSPC). To assess safety profiles, the researchers calculated number needed to harm (NNH) based on AE data with the use of darolutamide, apalutamide, or enzalutamide from the ARAMIS, SPARTAN, and PROSPER trials in patients with nmCRPC, and the ARANOTE, TITAN, and ARCHES trials in patients with mHSPC. NNH was calculated using reported rates of all-grade AEs, grade 3 or higher AEs, AEs of special interest, and AEs occurring in at least 5% of patients in the experimental (ARI plus ADT) and placebo (ADT) treatment arms of the trials. A higher NNH corresponded to a lower incremental likelihood of harm relative to the placebo arm. A negative NNH reflected a higher incremental risk (such as of an AE) in the placebo arm. In the studies of patients with nmCRPC, darolutamide was found to have a more favorable NNH than either apalutamide or enzalutamide in primary analyses of certain all-grade AEs. All-grade hypertension had an NNH value of 71.4 for darolutamide, 20.0 for apalutamide, and 14.3 for enzalutamide. The NNHs for all-grade falls were NEG, 15.2, and 14.3, respectively, and the NNHs for all-grade fatigue were 29.4, 10.8, and 5.3, respectively. Similar trends were reported for grade 3 or higher AEs. These patterns were maintained at final analyses, the researchers noted. In studies of patients with mHSPC, NNH values tended to be more favorable with darolutamide than with other ARIs for some all-grade AEs, such as rash, hypertension, and fatigue. However, all-grade constipation demonstrated NNH values of 45.5 with darolutamide and NEG with both apalutamide and enzalutamide. All-grade cognitive impairment was associated with a more favorable NNH with darolutamide than with the other ARIs in both nmCRPC and mHSPC, the researchers reported. There were minimal differences observed for seizures across the ARIs with either nmCRPC or mHSPC, and all-grade fractures demonstrated conflicting patterns. The researchers indicated that comparisons of NNH across these trials should be interpreted with caution due to heterogeneity in both study populations and study designs. They also noted that the study findings are descriptive. “In this NNH analysis of AE risk profiles of ARIs, darolutamide had a generally more favorable safety profile in nmCRPC and mHSPC, with favorable NNH statistics for most all-grade and grade ≥3 AEs compared with other ARIs,” the researchers concluded. “In nmCRPC, the favorable NNH for darolutamide was maintained over time.” Disclosures: This research was supported by Bayer. Some study authors disclosed conflicts of interest. Please see the original reference for complete disclosures. References: George DJ, Fizazi K, Morgans AK, et al. Evaluating safety: Number needed to harm analyses of androgen receptor inhibitors in advanced prostate cancer. Eur J Cancer. Published online August 8, 2026. doi:10.1016/j.ejca.2026.116982