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
Mené sur 14 patients atteints d'un cancer de la prostate résistant à la castration et de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la diminution du taux de PSA et du taux de réponse, et la toxicité du sélinexor, un inhibiteur de XPO1, après l'échec d'un traitement de seconde ligne par abiratérone et/ou enzalutamide (durée médiane de suivi : 4 mois)
Background : 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. Methods : 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. Results : Fourteen patients were enrolled. Selinexor was initially administered at 65 mg/m2 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. Conclusion : Selinexor demonstrated clinical activity and poor tolerability in mCRPC patients refractory to second‐line anti‐androgenic agents.
The Oncologist 2018