Darolutamide (AR antagonist) triplet delays mCRPC (HR 0.36) without worsening pain/QoL in mHSPC

Darolutamide is an oral androgen receptor (AR) antagonist evaluated as “triplet therapy” with androgen deprivation therapy (ADT) plus docetaxel in the Phase III ARASENS trial (NCT02799602) in metastatic hormone-sensitive prostate cancer (mHSPC). In 1,305 randomized patients (n=651 darolutamide; n=654 placebo), darolutamide significantly delayed time to metastatic castration-resistant prostate cancer (mCRPC) (HR 0.36, 95% CI 0.30–0.42) and time to pain progression (HR 0.79, 95% CI 0.66–0.95), while time to worsening of patient-reported pain interference/severity and NFPSI-17 symptom scores was similar between arms; TEAEs typically associated with AR pathway inhibition were generally low and similar with >3.5 years median follow-up (the OS benchmark for adding darolutamide to ADT+docetaxel in ARASENS was HR 0.68 vs ADT+docetaxel alone, while docetaxel itself historically improved OS vs ADT alone in CHAARTED: mOS 57.6 vs 47.2 months; HR 0.72).