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

Area of Science:

• Oncology
• Pharmacology

Background:

• Selinexor, an exportin-1 (XPO1) inhibitor, promotes nuclear accumulation of tumor suppressor proteins.
• Clinical activity of selinexor has been observed in endometrial cancer (EC).

Purpose of the Study:

• To assess the efficacy of once-weekly oral selinexor in improving progression-free survival (PFS) for patients with advanced or recurrent EC.
• The study aimed to evaluate selinexor as a maintenance therapy following chemotherapy in EC patients.

Main Methods:

• The ENGOT-EN5/GOG-3055/SIENDO study was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III trial.
• 263 patients with advanced or recurrent EC who completed chemotherapy and achieved response were randomized to receive selinexor (80 mg weekly) or placebo.
• The primary endpoint was progression-free survival (PFS).

Main Results:

• The overall intent-to-treat population did not meet the statistical significance for PFS improvement with selinexor versus placebo (median PFS 5.7 vs. 3.8 months; P=.126).
• An exploratory analysis using audited stratification data showed a statistically significant improvement in PFS for selinexor (HR=0.71; P=.049).
• In a prespecified subgroup of TP53 wild-type (wt) EC patients, selinexor demonstrated a median PFS of 13.7 months compared to 3.7 months for placebo.

Conclusions:

• While the primary endpoint was not met in the overall population, selinexor showed a trend towards improved PFS.
• Exploratory analyses, particularly in the TP53 wild-type subgroup, suggest a promising role for selinexor as maintenance therapy in specific EC patient populations.