Selinexor Improves PFS in Advanced or Recurrent Endometrial Cancer

The SIENDO (ENGOT-EN5/GOG-3055; NCT03555422) study met its primary end point of a statistically significant improvement in median progression-free survival (PFS) with maintenance selinexor (Xpovio) compared to placebo in patients with endometrial cancer, according to a presentation given during the March 2022 ESMO Virtual Plenary.¹

“Selinexor demonstrated a 30% decrease of risk for progression-free survival or death compared to placebo [HR, 0.705; 95% CI, 0.499-0.996] which was statistically significant,“ stated Professor Ignace Vergote, MD, PhD, principal investigator and gynecologic oncologist, ENGOT and the Belgium and Luxembourg Gynecological Oncology Group, University of Leuven, Leuven Cancer Institute.

Endometrial cancer is the most common gynecologic malignancy and options for advanced or recurrent disease after platinum-based therapy and/or radiotherapy are limited. Because the prognosis for this patient population remains poor, selinexor, a novel, oral selective inhibitor of nuclear export, has been evaluated to determine its efficacy and safety as a maintenance therapy following chemotherapy in patients with advanced or recurrent endometrial cancer in the phase 3 SIENDO study.

The multicenter, blinded, placebo-controlled, randomized study enrolled 263 patients with advanced stage IV endometrial cancer who had a partial or complete response after at least 12 weeks of standard taxane-platinum combination chemotherapy.² Prior surgery, radiotherapy, or hormonal therapy was allowed.

Participants were randomized 2:1 to receive either maintenance therapy with an oral dose of selinexor (n = 174) at 80 mg orally or placebo (n = 89) on days 1, 8, 15, and 22 of each 28-day cycle.

Enrollment was open to females aged 18 or older with histologically confirmed endometrial cancer. Baseline characteristics were evenly distributed between both arms with 65.6 years as the median age for participants in the selinexor arm and 64.0 years in the placebo arm. An ECOG performance status between 0-2 was found between each arm. In the selinexor group, 55.2% of the patients had endometrioid histology compared to 53.9% in the placebo group.

The study’s primary end point was PFS compared to placebo with secondary end points including disease-specific survival, overall survival (OS), time to first subsequent therapy, time to second subsequent therapy, PFS on subsequent therapy and safety and tolerability. The goal of the study was to demonstrate a hazard ratio (HR) of 0.6 or better.

Findings revealed patients with all of the stratification factors treated with selinexor to have a median PFS of 5.7 months (95% Cl, 3.81-9.20) compared to 3.8 months (95% Cl, 3.68-7.39) for patients on placebo (HR, 0.705).

Vergote discussed his interest in the subgroups’ PFS based on histological subtypes which were based on audited stratification factors. For patients with endometrioid cancer, PFS was 9.2 months when given selinexor versus 3.8 months with placebo (95% CI, 0.348-0.944). For patients with serous histology, PFS was 3.8 months in the selinexor arm compared to 3.7 months in the placebo arm (95% CI, 0.481-1.533).

As for patients with wild type P53 endometrial cancer, median PFS in the selinexor group (n = 67) was 13.7 months (95% CI, 9.20 to not reached) and 3.7 months (95% CI, 1.87-12.88) in the placebo group (n = 36), resulting in a 62% reduction in the risk for progression and/or death with selinexor compared to placebo (HR, 0.38; 95% CI, 0.210-0.670). QOL data were similar between both groups.

In regard to safety, selinexor was well tolerated and no new safety signals were identified. The study had a low discontinuation rate of 10.5% in the selinexor arm versus 1% in the placebo arm due to adverse events (AEs). No deaths were reported in either arm.

Some treatment-emergent adverse events (TEAEs) occurred in patients who received selinexor included nausea (10%), neutropenia (9%), thrombocytopenia (6%), asthenia (6%), fatigue (6%), and anemia (5%). Only 1 patient reported a grade 4 TEAE of thrombocytopenia. There were no cases of severe bleeding in patients with thrombocytopenia and no cases of febrile neutropenia.

OS data are immature and the final OS analysis is expected in early 2023.

References:

1. Vergote I. 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.

2. Maintenance with selinexor/placebo after combination chemotherapy in participants with endometrial cancer [SIENDO] (ENGOT-EN5). ClinicalTrials.gov. Updated January 28, 2022. Accessed February 8, 2022. https://clinicaltrials.gov/ct2/show/NCT03555422