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

Medientyp: E-Artikel
Titel: Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer
Beteiligte: Vergote, Ignace; Pérez-Fidalgo, Jose Alejandro; Hamilton, Erika Paige; Valabrega, Giorgio; Van Gorp, Toon; Sehouli, Jalid; Cibula, David; Levy, Tally; Welch, Stephen; Richardson, Debra L.; Guerra, Eva M.; Scambia, Giovanni; Henry, Stéphanie; Wimberger, Pauline; Miller, David S.; Klat, Jaroslav; Martínez-Garcia, Jerónimo; Raspagliesi, Francesco; Pothuri, Bhavana; Romero, Ignacio; Bergamini, Alice; Slomovitz, Brian; Schochter, Fabienne; Høgdall, Estrid; [...]
Erschienen: American Society of Clinical Oncology (ASCO), 2023
Erschienen in: Journal of Clinical Oncology
Sprache: Englisch
DOI: 10.1200/jco.22.02906
ISSN: 0732-183X; 1527-7755
Entstehung:
Anmerkungen:
Beschreibung: <jats:sec><jats:title>PURPOSE</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>PATIENTS AND METHODS</jats:title><jats:p> 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 ). </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> 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%). </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> 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. </jats:p></jats:sec>

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: