Maintenance Selinexor Improves PFS Vs Placebo in Advanced or Recurrent Endometrial Cancer

Maintenance selinexor (Xpovio) monotherapy was found to improve progression-free survival (PFS) over placebo in patients with advanced or recurrent endometrial cancer, according to data from the phase 3 SIENDO/ENGOT-EN5/GOG-3055 study (NCT03555422) which were presented during the 2022 SGO Annual Meeting on Womens’ Cancers.

Investigators reported a median progression-free survival (PFS) of 5.7 months (95% CI, 3.81-9.20) in the selinexor group vs 3.8 months (95% CI, 3.68-7.39) in the placebo group in the intent-to-treat population (ITT; HR, 0.705; 95% CI, 0.499-0.996; one-sided P = .024). In the selinexor and placebo groups, respectively, the PFS rate at 3 months was 72.4% vs 66.4%, 48.2% vs 40.9% at 6 months, 41.7% vs 34.1% at 9 months, and 35.3% vs 25.8% at 12 months.

When assessing PFS in patients by histologic subtype in the pre-specified exploratory analysis, patients with endometrioid carcinoma achieved a PFS of 9.2 months with selinexor and 3.8 months with placebo (HR, 0.573; 95% CI, 0.348-0.944; one-sided P = .014). Additionally, those with serous histology had a median PFS of 3.8 months and 3.7 months with each respective treatment (HR, 0.859; 95% CI, 0.481-1.533; P = .309). Additionally, in patients with wild-type p53 endometrial cancer, the median PFS was 13.7 months (95% CI, 9.20–not reached) in the selinexor arm and 3.7 months in the placebo arm (95% CI, 1.87-12.88; HR, 0.375; 95% CI, 0.210-0.670; one sided P = .0003).

“Selinexor demonstrated in the audited ITT population a 30% decrease in risk for progression and/or death compared with the placebo, but this was not significant in the non-audited population,” Ignace B. Vergote, MD, PhD, head of the Department of Obstetrics and Gynecology and Gynecologic Oncology, Catholic University of Leuven, Belgium.

Investigators enrolled patients with stage IV disease or who on their first relapse, including those with endometrioid, serous, undifferentiated, or carcinosarcoma histology. Patients needed to have at least 12 weeks of treatment with taxane and carboplatin followed by a partial response (PR) or complete response (CR). Previous surgery, radiotherapy, or hormonal therapy were allowed.

Patients were randomized 2:1 to receive either 80 mg of selinexor weekly until progressive disease (n = 174) or placebo (n = 89). The primary end point of the trial was investigator assessed PFS and key secondary end points included overall survival, PFS by blinded independent central review, and disease control rate. Pre-defined exploratory end points included histological subtype and molecular subclassification.

In the selinexor cohort, 33.3% of patients were 70 years or older and most patients had an ECOG performance status of 0 (56.9%) or 1 (40.8%). The majority of patients had endometrioid (55.2%) and serous (28.2%) histology. At the time of treatment with the combination chemotherapy regimen, most patients had recurrent disease (55.2%) and 44.8% had stage IV disease. Additionally, 59.8% had a PR and 40.2% had a CR following most recent chemotherapy.

Additionally, in the placebo cohort, 31.5% of patients were 70 years or older, all of whom had an ECOG performance status of 0 (60.7%) and 1 (39.3%). Most patients in the cohort had endometrioid (53.9%) and serous (31.5%) histology. Moreover, 51.7% of patients had recurrent disease and 48.3% had stage IV disease at the time of combination chemotherapy. After the most recent chemotherapy treatment, 55.1% of patients had a PR and 44.9% had a CR.

Notably, investigators stated that stratification factor of CR and PR was incorrect for 7 patients and was corrected before the database's lock and unblinding. The median follow-up was 10.2 months (95% CI, 8.97-13.57).

In terms of safety, the most common any grade treatment-emergent adverse effects (TEAEs) in the selinexor arm were nausea (84%), vomiting (52%), constipation (37%), and thrombocytopenia (37%) and grade 3/4 TEAEs included nausea (10%), neutropenia (9%), asthenia (6%), fatigue (6%), and thrombocytopenia (6%). For the placebo group, common any grade TEAEs included constipation (38%), nausea (34%), diarrhea (23%), and asthenia (21%) and grade 3/4 TEAEs included constipation (2%), nausea (1%), vomiting (1%), fatigue (1%), and asthenia (1%).

Moreover, in the selinexor arm, 49.7% of patients required a dose reduction, 51.5% needed a dose interruption, and 10.5% discontinued. For patients treated with placebo, 3.4% needed a dose reduction, 18.2% had a dose interruption, and 1.1% discontinued. No TEAEs led to death in either arm.

In terms of patient-reported quality of life, investigators did not observe any significant differences in global health, physical functioning, or symptoms.

Reference

1. Vergote I, Pérez Fidalgo A, Hamilton E, et al. SIENDO/ENGOT-EN5/GOG-3055: a randomized phase 3 trial of maintenance selinexor versus placebo after combination platinum-based chemotherapy in advanced or recurrent endometrial cancer. Presented at: 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022. Phoenix, Arizona. Abstract 249.