A Phase II Trial of Selinexor, an Oral Selective Inhibitor of Nuclear Export Compound, in Abiraterone- and/or Enzalutamide-Refractory Metastatic Castration-Resistant Prostate Cancer

BackgroundSelinexor 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. MethodsThis 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. ResultsFourteen patients were enrolled. Selinexor was initially administered at 65 mg/m(2) twice a week (days 1 and 3) and was subsequently reduced to 60 mg flat dose twice a week (days 1 and 3), 3 weeks on, 1 week off, to improve tolerability. The median treatment duration was 13 weeks. At a median follow-up of 4 months, two patients (14%) had 50% prostate-specific antigen (PSA) decline, and seven patients (50%) had any PSA decline. Of eight patients with measurable disease at baseline, two (25%) had a partial response and four (50%) had stable disease as their best radiographic response. Five patients (36%) experienced serious adverse events (SAEs; all unrelated to selinexor), and five patients (36%) experienced treatment-related grade 3-4 AEs. The most common drug-related adverse events (AEs) of any severity were anorexia, nausea, weight loss, fatigue, and thrombocytopenia. Three patients (21%) came off study for unacceptable tolerability. ConclusionSelinexor demonstrated clinical activity and poor tolerability in mCRPC patients refractory to second-line anti-androgenic agents.