Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Universitair Ziekenhuis (UZ) Leuven
  • Hospital Clinico Universitario de Valencia
  • Sarah Cannon Research Institute and Tennessee Oncology
  • Polytechnic University of Turin
  • Charité – Universitätsmedizin Berlin
  • Allgemeine Fakultätskrankenhaus Prag
  • Tel Aviv University
  • London Health Sciences Centre
  • University of Oklahoma
  • Hospital Ramon y Cajal
  • Mito Kyodo General Hospital
  • CHU UCL Namur Site Ste Elisabeth
  • University of Texas Southwestern Medical Center
  • Fakultní nemocnice Ostrava
  • Hospital Virgen de la Arrixaca
  • IRCCS Fondazione Istituto Neurologico Casimiro Mondino - Pavia
  • New York University
  • Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
  • Florida International University
  • Universitätsklinikum Ulm
  • Copenhagen University Hospitals
  • Hospital Universitari Vall d'Hebron
  • Creighton University
  • Karyopharm Therapeutics
  • Weill Cornell Medical College in Qatar
  • Fundación Instituto Valenciano de Oncología

Abstract

PURPOSE: Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer (EC). The primary end point was to assess progression-free survival (PFS) with once-weekly oral selinexor in patients with advanced or recurrent EC.

PATIENTS AND METHODS: ENGOT-EN5/GOG-3055/SIENDO was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III study at 107 sites in 10 countries. Patients 18 years or older with histologically confirmed EC were enrolled. All had completed a single line of at least 12 weeks of taxane-platinum combination chemotherapy and achieved partial or complete response. Patients were assigned to receive 80 mg oral selinexor once weekly or placebo with 2:1 random assignment (ClinicalTrials.gov identifier: NCT03555422).

RESULTS: Between January 2018 and December 2021, 263 patients were randomly assigned, with 174 allocated to selinexor and 89 to placebo. The median PFS was 5.7 months (95% CI, 3.81 to 9.20) with selinexor versus 3.8 months (95% CI, 3.68 to 7.39) with placebo (hazard ratio [HR], 0.76 [95% CI, 0.54 to 1.08]; two-sided P = .126), which did not meet the criteria for statistical significance in the intent-to-treat population. Incorrect chemotherapy response stratification data for 7 (2.7%) patients were identified. In a prespecified exploratory analysis of PFS in audited stratification data, PFS for selinexor met the threshold for statistical significance (HR, 0.71; 95% CI, 0.499 to 0.996; two-sided P = .049). Furthermore, patients with the TP53 wild-type (wt) EC had a median PFS of 13.7 and 3.7 months with selinexor and placebo. The most common grade 3 treatment-related adverse events were nausea (9%), neutropenia (9%), and thrombocytopenia (7%).

CONCLUSION: The significance level for PFS was only met in the audited analysis. However, a preliminary analysis of a prespecified exploratory subgroup of patients with TP53wt EC showed promising results with selinexor maintenance therapy.

Details

OriginalspracheEnglisch
Seiten (von - bis)5400-5410
Seitenumfang25
FachzeitschriftJournal of Clinical Oncology
Jahrgang41
Ausgabenummer35
Frühes Online-Datum5 Sept. 2023
PublikationsstatusVeröffentlicht - 10 Dez. 2023
Peer-Review-StatusJa

Externe IDs

Scopus 85173883633
Mendeley a3185c7b-5e13-3425-92ae-d2510214e0cb

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Prospective Studies, Double-Blind Method, Triazoles/adverse effects, Humans, Endometrial Neoplasms/drug therapy, Female, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Hydrazines/adverse effects

Bibliotheksschlagworte