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Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer
I. Vergote, JA. Pérez-Fidalgo, EP. Hamilton, G. Valabrega, T. Van Gorp, J. Sehouli, D. Cibula, T. Levy, S. Welch, DL. Richardson, EM. Guerra, G. Scambia, S. Henry, P. Wimberger, DS. Miller, J. Klat, J. Martínez-Garcia, F. Raspagliesi, B. Pothuri,...
Language English Country United States
Document type Randomized Controlled Trial, Multicenter Study, Clinical Trial, Phase III, Journal Article
NLK
Free Medical Journals
from 2004 to 1 year ago
Open Access Digital Library
from 1999-01-01
PubMed
37669480
DOI
10.1200/jco.22.02906
Knihovny.cz E-resources
- MeSH
- Double-Blind Method MeSH
- Hydrazines * adverse effects MeSH
- Humans MeSH
- Endometrial Neoplasms * drug therapy MeSH
- Prospective Studies MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects MeSH
- Triazoles adverse effects MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
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.
BGOG Leuven Cancer Institute University Hospitals Leuven Leuven Belgium
Department of Gynecology and Obstetrics University Hospital Ulm Ulm Germany
Department of Obstetrics and Gynecology San Raffaele Milano Milano Italy
Department of Oncology GEICO Hospital Universitario Virgen de la Arrixaca Murcia Spain
Department of Pathology Herlev Hospital Copenhagen University Hospital Copenhagen Denmark
Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy
GEICO Hospital Universitario Ramon y Cajal Madrid Spain
GOG HonorHealth University of Arizona Creighton University Phoenix AZ
INCLIVA CIBERONC GEICO Hospital Clinico Universitario de Valencia Spain
Karyopharm Therapeutics Newton MA
London Health Sciences Centre London ON Canada
Medical Oncology Fundacion Instituto Valenciano de Oncologia Valencia Spain
Memorial Sloan Kettering Cancer Center Weill Cornell Medical College New York NY
MITO and Department of Oncology University of Torino Mauriziano Hospital Turin Italy
MITO Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy
Mount Sinai Medical Center Florida International University Miami FL
NYU Langone Health Perlmutter Cancer Center New York University School of Medicine New York NY
Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Sarah Cannon Research Institute and Tennessee Oncology Nashville TN
Stephenson Cancer Center University of Oklahoma Health Sciences Center Oklahoma City OK
Università Vita Salute San Raffaele Milano Italy
University Hospital Ostrava and University of Ostrava Ostrava Poruba Czech Republic
References provided by Crossref.org
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