Second-generation androgen receptor inhibitors in therapy of non-metastatic castration resistant prostate cancer: role of safety profile and effect on quality of life

Abstract

The article discusses the role of second-generation androgen receptor inhibitors (ARi) in therapy of non-metastatic castration resistant prostate cancer (nmCRPC). The phase 3 trials PROSPER (enzalutamide), SPARTAN (apalutamide) and ARAMIS (darolutamide) showed that these medicines if used in combination with androgen deprivation therapy (ADT) make possible to significantly improve, as compared with placebo, metastasis-free survival and overall survival of patients with nmCRPC. An important role in choosing a certain medicine of the group is played by its safety profile, including its drug-drug interaction potential and effect on patient’s quality of life. In this respect, darolutamide has a number of advantages over apalutamide or enzlutamide. The frequency of CNS (cognitive, psychiatric, convulsive) and other adverse drug reactions that significantly worsen the patients’ quality of life (falls, fractures, hypertension, etc.) in therapy with darolutamide does not differ from that with placebo. Moreover, this medicine retains its antagonistic effects to all clinically significant androgen receptor mutations that develop resistance to enzalutamide and apalutamide.