Results presented at an ESMO Virtual Plenary in March 2022 show that maintenance therapy with selinexor decreased the risk of progression or death for patients with advanced or recurrent endometrial cancer.
Maintenance therapy with once-weekly selinexor (Xpovio) following combination chemotherapy led to a statistically significant decrease in the risk of progression or death compared with placebo for patients with advanced or recurrent endometrial cancer, according to results from the phase 3 ENGOT-EN5/GOG-3055/SIENDO study (NCT03555422) presented at the European Society for Medical Oncology Virtual Plenary held on March 17, 2022.
In the audited intent-to treat (ITT) population, median investigator-assessed progression-free survival (PFS) was 5.7 months (95% CI, 3.81-9.20) in the selinexor group (n = 174) compared with 3.8 months (95% CI, 3.68-7.39) in the placebo group (n = 89; HR, 0.705; 95% CI, 0.499-0.996; P = .024).
“It’s important to note that the [Kaplan-Meier] curves split around 5 months and then the difference stays between the 2 arms,” Ignace Vergote, MD, PhD, Chairman of the Leuven Cancer Institute and department head of Obstetrics and Gynecology and Gynecologic Oncology at the Catholic University of Leuven in Belgium, explained in a presentation of the data. “It is also important to note that this is an analysis on the audited stratification factors.”
Patients who had previous taxane/carboplatin for at least 12 weeks with stage IV endometrial cancer or disease in first relapse were enrolled. Prior surgery, radiotherapy or hormonal therapy was allowed.
Patients who experienced a complete or partial response to first-line chemotherapy per RECIST version 1.1 were randomized 2:1 to receive weekly selinexor at 80 mg until progression or matching placebo. Patients in the selinexor group who had a body mass index below 20 received 60 mg of treatment.
The primary end point was investigator-assessed PFS. Secondary end points included overall survival (OS), PFS per blinded independent review committee, patient-reported outcomes (PROs), time to first subsequent therapy, time to second subsequent treatment, PFS on subsequent therapy (PFS2), disease-specific survival, and disease control rate (DCR).
Of the 174 patients in the selinexor group, 171 received at least 1 dose of treatment and 111 discontinued treatment. Disease progression was observed in 75 patients and 15 patients withdrew from the trial. For the 89 patients in the placebo group, 88 received at least 1 dose of selinexor, 52 discontinued treatment, 50 experienced disease progression, and no patients withdrew.
At the end of study disposition, 120 and 65 patients in the selinexor and placebo groups, respectively, remained on study. At this point, 42 deaths were observed in the selinexor group vs 22 in the placebo group. Median follow up was 10.2 months.
In the selinexor group, median age was 65.5 years. Most patients were under the age of 70 years (66.7%), had an ECOG performance status of 0 (56.9%), had 1 prior antineoplastic regimen (98.9%), and presented with endometrioid histology (55.2%). After the most recent chemotherapy, 40.2% of patients experienced a complete response and 59.8% had a partial response.
In the placebo group, median age was 64.0 years. Most patients were less than 70 years of age (68.5%), had an ECOG performance status of 0 (60.7%), had 1 prior antineoplastic regimen (95.5%), and had endometrioid histology (53.9%). After the most recent chemotherapy, 44.9% of responses were complete and 55.1% were partial.
More than half of the patients, specifically 55.2% in the selinexor group vs 51.7% in the placebo group, had recurrent disease.
When analyzing probability of PFS by different subgroups, selinexor significantly improved PFS over placebo for patients with endometrioid carcinoma (9.2 months vs 3.8 months; HR, 0.573; 95% CI, 0.348-0.944; P = .014). A significant improvement was also observed with selinexor over placebo (13.7 months vs 3.7 months, respectively) for patients with TP53 wildtype endometrioid carcinoma (HR, 0.375; 95% CI, 0.210-0.670; P = .0003).
Treatment-emergent adverse effects (TEAEs) of any grade in the selinexor group seen in more than 20% of patients included nausea (84%), vomiting (52%), constipation (37%), thrombocytopenia (37%), decreased appetite (35%), fatigue (35%), diarrhea (34%), asthenia (31%), anemia (28%), and neutropenia (25%). Grade 3 TEAEs in more than 2% of patients included nausea (10%), vomiting (2%), thrombocytopenia (6%), fatigue (6%), diarrhea (2%), asthenia (6%), anemia (5%), neutropenia (9%), and abdominal pain (2%). One case of grade 4 cytopenia was observed.
In the placebo group, any-grade TEAEs occurring in more than 20% of patients were nausea (34%), constipation (38%), diarrhea (23%), and asthenia (21%). Constipation (2%) was the only grade 3 TEAE seen in more than 2% of patients.
TEAEs leading to dose reductions occurred in 49.7% of patients in the selinexor group and 3.4% of patients in the placebo group. Dose interruptions occurred in 51.5% and 18.2% of patients in the selinexor and placebo groups, respectively. Discontinuations were seen in 10.5% of patients in the selinexor group and 1.1% of patients in the placebo group. No treatment-related deaths were observed.
Vergote I, 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 2022; March 16-18, 2022.