Selinexor maintenance prolongs progression-free survival (PFS), when compared with placebo, in patients with advanced or recurrent endometrial cancer, according to results of the phase 3 SIENDO study.
Selinexor was associated with a 30% decrease in the risk of progression or death, said Ignace B. Vergote, MD, PhD, of the Catholic University of Leuven in Belgium. Dr Vergote presented these results in an ESMO Virtual Plenary presentation.
SIENDO is a phase 3 study (ClinicalTrials.gov Identifier: NCT03555422) designed to investigate the efficacy of selinexor as maintenance therapy in patients with stage IV endometrial cancer or a first relapse of disease who achieved partial or complete remission after taxane-platinum combination therapy.
The study enrolled 263 patients with endometrioid, serous, undifferentiated, or carcinosarcoma histology. The patients were randomly assigned to receive selinexor (n=174) or placebo (n=89) until disease progression. Baseline characteristics were well-balanced between the treatment arms.
The median follow-up was 10.2 months. The median PFS was 5.7 months in the selinexor arm and 3.8 months in the placebo arm (hazard ratio [HR], 0.705; 95% CI, 0.499-0.996; P =.024).
Subgroup analyses showed a PFS benefit with selinexor among patients with endometrioid histology and those with wild-type TP53. Among patients with endometrioid histology, the median PFS was 9.2 months with selinexor and 3.8 months with placebo (HR, 0.573; 95% CI, 0.348- 0.944; P =.014). Among patients with wild-type TP53, the median PFS was 13.7 months and 3.7 months, respectively (HR, 0.375; 95% CI, 0.210-0.670; P =.0003).
Dr Vergote noted that the overall survival (OS) data are immature, and the final OS analysis is expected in early 2023.
The most common adverse events (in the selinexor and placebo arms, respectively) were nausea (84% vs 34%), vomiting (52% vs 17%), and constipation (37% vs 38%).
Adverse events associated with selinexor were generally manageable with supportive care and dose modifications, Dr Vergote said. He added that no new safety signals were identified during the study.
Disclosures: This research was supported by Karyopharm Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Vergote IB, Fidalgo AP, Hamilton E, et al. Prospective double-blind, randomized phase III ENGOT-EN5/GOG-3055/SIENDO study of oral selinexor/placebo as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer. Presented at ESMO Virtual Plenary; March 17, 2022. Abstract VP2-2022.