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

CEEGOG 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

CHU UCL Namur Site Ste Elisabeth Service d'onco hématologie BGOG and Université Catholique de Louvain Namur Belgium

Department of Gynecology and Obstetrics University Hospital Ulm Ulm Germany

Department of Gynecology NOGGO European Competence Center for Ovarian Cancer Charité Comprehensive Cancer Center Charité Berlin University of Medicine Berlin Germany

Department of Obstetrics and Gynecology San Raffaele Milano Milano Italy

Department of Obstetrics and Gynecology University Hospital Carl Gustav Carus NOGGO and Technische Universitat Dresden Dresden Germany

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

Gynaecologic Cancer Programme Vall d'Hebron Institute of Oncology Hospital Universitari Vall d'Hebron Barcelona Spain

Gynecologic Oncology Unit Department of Obstetrics and Gynecology ISGO Wolfson Medical Center Affiliated with Sackler Faculty of Medicine Tel Aviv University Holon Israel

Harold C Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center Dallas TX

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

Citace poskytuje Crossref.org

ENGOT-EN20/GOG-3083/XPORT-EC-042 - A phase III, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma: rationale, methods, and trial design

Zobrazit více v PubMed

ClinicalTrials.gov
NCT03555422