Selinexor Maintenance Therapy Improved PFS Among Patients With TP53 Wild-Type Advanced or Recurrent Endometrial Cancer

According to results from a prespecified exploratory analysis of audited stratification data from the ENGOT-EN5/GOG-3055/SIENDO study, selinexor maintenance therapy significantly improved progression-free survival (PFS) among patients with TP53 wild-type [TP53wt] advanced or recurrent endometrial cancer.

“Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer,” stated Ignace Vergote, MD, Leuven Cancer Institute, University of Leuven, Belgium, and coauthors. However, results from previous studies have found that “the significance level for PFS was only met in the audited analysis.”

In this prospective, placebo-controlled study, patients with advanced or recurrent endometrial cancer who achieved partial or complete response with a single-line of taxane-platinum combination chemotherapy were randomized on a 2-to-1 basis to receive either 80 mg selinexor once weekly (n = 174) or placebo (n = 89) between January 2018 and December 2021. The primary end point was PFS.

At the data cutoff point, median PFS was 5.7 months in the selinexor arm and 3.8 months in the placebo arm (hazard ratio [HR], 0.76; confidence interval [CI] 95%, 0.54 to 1.08; two-sided P = .126), which did not meet the criteria for statistical significance, and incorrect chemotherapy response stratification data was identified for 7 patients. In a prespecified exploratory analysis of PFS in audited stratification data, the threshold for statistical significance was met in the selinexor arm (HR, 0.71; 95% CI, 0.499 to 0.996; two-sided P = .049). Among patients with TP53wt endometrial cancer, median PFS was 13.7 months in the selinexor arm and 3.7 months in the placebo arm. The most common grade 3 treatment-related adverse events were nausea (9%), neutropenia (9%), and thrombocytopenia (7%). 

As concluded by Dr Vergote and coauthors, even though “the significance level for PFS was only met in the audited analysis… a preliminary analysis of a prespecified exploratory subgroup of patients with TP53wt [endometrial cancer] showed promising results with selinexor maintenance therapy.” 

“A randomized clinical trial using selinexor as maintenance therapy for participants with p53 wild-type advanced or recurrent endometrial is currently underway,” added associate editor of Journal of Clinical Oncology, Gini F. Fleming, MD, University of Chicago Medicine, Chicago, Illinois. 

Source:

Vergote I, Perez-Fidalgo JA, Hamilton EP, et al. Oral selinexor as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer. J Clin Oncol. Published online: September 5, 2023. doi:10.1200/JCO.22.02906