Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies

Gynecol Oncol. 2020 Feb;156(2):308-314. doi: 10.1016/j.ygyno.2019.11.012. Epub 2019 Dec 9.

Abstract

Background: Selinexor is an oral inhibitor of the nuclear export protein Exportin 1 (XPO1) with demonstrated antitumor activity in solid and hematological malignancies. We evaluated the efficacy and safety of selinexor in heavily pretreated, recurrent gynecological malignancies.

Methods: In this phase 2 trial, patients received selinexor (35 or 50 mg/m2 twice-weekly [BIW] or 50 mg/m2 once-weekly [QW]) in 4-week cycles. Primary endpoint was disease control rate (DCR) including complete response (CR), partial response (PR) or stable disease (SD) ≥12 weeks. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety.

Results: 114 patients with ovarian (N = 66), endometrial (N = 23) or cervical (N = 25) cancer were enrolled. Median number of prior regimens for ovarian, endometrial and cervical cancer was 6 (1-11), 2 (1-5), and 3 (1-6) respectively. DCR was 30% (ovarian 30%; endometrial 35%; cervical 24%), which included confirmed PRs in 8%, 9%, and 4% of patients with ovarian, endometrial, and cervical cancer respectively. Median PFS and OS for patients with ovarian, endometrial and cervical cancer were 2.6, 2.8 and 1.4 months, and 7.3, 7.0, and 5.0 months, respectively. Common Grade 3/4 adverse events (AEs) were thrombocytopenia (17%), fatigue (14%), anemia (10%), nausea (9%) and hyponatremia (9%). Patients with ovarian cancer receiving 50 mg/m2 QW had fewer high-grade AEs with similar efficacy as BIW treatment.

Conclusions: Selinexor demonstrated single-agent activity and disease control in patients with heavily pretreated ovarian and endometrial cancers. Side effects were a function of dose level and treatment frequency, similar to previous reports, reversible and mitigated with supportive care.

Trial registration: ClinicalTrials.gov NCT02025985.

Keywords: Cervical cancer; Endometrial cancer; Ovarian cancer; Selinexor; XPO1.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Female
  • Genital Neoplasms, Female / drug therapy*
  • Genital Neoplasms, Female / metabolism
  • Genital Neoplasms, Female / pathology
  • Humans
  • Hydrazines / administration & dosage*
  • Hydrazines / adverse effects
  • Karyopherins / antagonists & inhibitors*
  • Karyopherins / metabolism
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Progression-Free Survival
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects

Substances

  • Hydrazines
  • Karyopherins
  • Receptors, Cytoplasmic and Nuclear
  • Triazoles
  • exportin 1 protein
  • selinexor

Associated data

  • ClinicalTrials.gov/NCT02025985