In a phase III study (ENGOT-EN5/GOG-3055/SIENDO) reported in the Journal of Clinical Oncology, Ignace B. Vergote, MD, PhD, and colleagues found that a progression-free survival benefit with maintenance selinexor vs placebo after first-line chemotherapy in patients with advanced or recurrent endometrial cancer was significant only in the analysis of audited stratification data. A notable benefit of selinexor was observed among patients with TP53 wild-type disease.
Ignace B. Vergote, MD, PhD
Study Details
In the double-blind trial, 263 patients from sites in 10 countries who had partial or complete response after a single line of at least 12 weeks of taxane/platinum combination chemotherapy were randomly assigned 2:1 between January 2018 and December 2021 to receive selinexor at 80 mg (n = 174) or placebo (n = 89) once weekly until disease progression or treatment discontinuation. The primary endpoint of the trial was progression-free survival.
Progression-Free Survival
Median follow-up at data cutoff was 10.2 months (95% confidence interval [CI] = 8.97–13.57 months). Median progression-free survival was 5.7 months (95% CI = 3.81–9.20 months) in the selinexor group vs 3.8 months (95% CI = 3.68–7.39 months) in the placebo group (hazard ratio [HR] = 0.76, 95% CI = 0.54–1.08, P = .126); rates at 3, 6, and 12 months were 72% vs 66%, 48% vs 41%, and 35% vs 26%, respectively. The investigators identified incorrect chemotherapy response stratification data for seven patients (2.7%); in a prespecified exploratory analysis of audited stratification data, patients in the selinexor group had significantly improved progression-free survival vs those receiving placebo (HR = 0.71, 95% CI = 0.499–0.996, P = .049).
Among 103 patients (67 vs 36) with TP53 wild-type disease, median progression-free survival was 13.7 months in the selinexor group vs 3.7 months in the placebo group (HR = 0.41, 95% CI = 0.23–0.72, P = .002).
KEY POINTS
- Selinexor did not significantly improve progression-free survival on intent-to-treat analysis, but did so upon audited analysis.
- A significant benefit of selinexor was observed among patients with TP53 wild-type disease.
Adverse Events
The most common treatment-related adverse events of any grade in the selinexor group were nausea (80% vs 28% in placebo group), vomiting (50% vs 9%), and thrombocytopenia (36% vs 0%). The most common treatment-related grade 3 or 4 adverse events (only one grade 4 event was reported) in the selinexor group were nausea (9% vs 0%), neutropenia (9% vs 0%), and thrombocytopenia (7% vs 0%). Serious treatment-related adverse events occurred in 2.3% vs 0% of patients. Treatment-related adverse events led to treatment discontinuation in 10% vs 1% of patients.
The investigators concluded, “The significance level for progression-free survival was only met in the audited analysis. However, a preliminary analysis of a prespecified exploratory subgroup of patients with TP53 wild-type endometrial cancer showed promising results with selinexor maintenance therapy.”
Dr. Vergote, of Belgium and Luxembourg Gynaecological Oncology Group, Leuven Cancer Institute, University Hospitals Leuven, Belgium, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Karyopharm Therapeutics Inc. For full disclosures of the study authors, visit ascopubs.org.
