selinexor and abiraterone

In abiraterone- and/or enzalutamide-refractory metastatic castration-resistant prostate cancer (mCRPC) patients, selinexor led to prostate-specific antigen and/or radiographic responses in a subset of patients, indicating clinical activity in this indication.Despite twice-a-week dosing and maximal symptomatic management, selinexor was associated with significant anorexia, nausea, and fatigue in mCRPC patients refractory to second-generation anti-androgen therapies, limiting further clinical development in this patient population.This study highlights the challenge of primary endpoint selection for phase II studies in the post-abiraterone and/or post-enzalutamide mCRPC space.. Selinexor is a first-in-class selective inhibitor of nuclear export compound that specifically inhibits the nuclear export protein Exportin-1 (XPO-1), leading to nuclear accumulation of tumor suppressor proteins.. This phase II study evaluated the efficacy and tolerability of selinexor in patients with metastatic castration-resistant prostate cancer (mCRPC) refractory to abiraterone and/or enzalutamide.. Fourteen patients were enrolled. Selinexor was initially administered at 65 mg/m. Selinexor demonstrated clinical activity and poor tolerability in mCRPC patients refractory to second-line anti-androgenic agents.

Topics: Aged; Androstenes; Benzamides; Humans; Hydrazines; Male; Middle Aged; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms, Castration-Resistant; Triazoles