Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
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
- Centre Hospitalier Universitaire UCL Namur
- 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
Originalsprache | Englisch |
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Seiten (von - bis) | 5400-5410 |
Seitenumfang | 25 |
Fachzeitschrift | Journal of Clinical Oncology |
Jahrgang | 41 |
Ausgabenummer | 35 |
Frühes Online-Datum | 5 Sept. 2023 |
Publikationsstatus | Veröffentlicht - 10 Dez. 2023 |
Peer-Review-Status | Ja |
Externe IDs
Scopus | 85173883633 |
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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