Maintenance selinexor promising for PFS in advanced/recurrent endometrial cancer

Maintenance treatment with selinexor improved progression-free survival (PFS) in patients with advanced or recurrent endometrial cancer who had previously received first-line chemotherapy, particularly those with endometrioid histology and wild-type p53, according to a study presented at SGO 2022.

“Selinexor demonstrated … a 30 percent decrease in the risk for progression and/or death compared with placebo,” said study author Professor Ignace Vergote from the Catholic University Leuven and Cancer Institute at University Hospitals, Belgium.

The phase III ENGOT-EN5/GOG-3055/SIENDO study involved patients with stage IV or first recurrence of endometrial cancer who had partial or complete response to ≥12 weeks of taxane-carboplatin chemotherapy. They were randomized 2:1 to receive selinexor (80 mg QW, or 60 mg QW for those with BMI <20 kg/m²; n=174) or placebo (n=89) until disease progression.

The median age of the participants was 64–66 years, most patients had ECOG performance status 0 (56.9 and 60.7 percent in the selinexor and placebo groups, respectively) or 1 (40.8 and 39.3 percent, respectively), and about half the population (54–55 percent) had endometrioid tumours. Almost all patients had received only one prior antineoplastic treatment regimen. Fifty-five and 52 percent of patients in the selinexor and placebo groups, respectively, had recurrent disease, and 60 and 55 percent, respectively, had partial response to prior treatment.

After a median follow-up of 10.2 months, PFS in the intention-to-treat population was improved by 30 percent with selinexor vs placebo (median 5.7 vs 3.8 months; hazard ratio [HR], 0.705, 95 percent confidence interval [CI], 0.499–0.996; p_one-sided=0.024).

In a subgroup analysis according to histologic type, the PFS benefits of selinexor over placebo were evident specifically among those with endometrioid carcinoma (median 9.2 vs 3.8 months; HR, 0.573, 95 percent CI, 0.348–0.944; p_one-sided=0.014) and not among those with serous tumours (median 3.8 vs 3.7 months; HR, 0.859, 95 percent CI, 0.481–1.533; p_one-sided=0.309).

The PFS benefit with selinexor vs placebo was also noted in a prespecified exploratory analysis of the 103 patients with wild-type p53 endometrial carcinoma (median 13.7 vs 3.7 months; HR, 0.375, 95 percent CI, 0.210–0.670; p_one-sided=0.0003).

The most common (≥2 percent) grade 3 treatment-emergent adverse events (TEAEs) among selinexor recipients were nausea (10 percent), neutropenia (9 percent), and thrombocytopenia, fatigue, and asthenia (6 percent each), while the most common in placebo recipients was constipation (2 percent). There was one grade 4 thrombocytopenia event in the selinexor group. There were no cases of febrile neutropenia or severe bleeding in patients with thrombocytopenia.

TEAEs led to dose reduction in 49.7 and 3.4 percent of selinexor and placebo recipients, respectively, dose interruption in 51.5 and 18.2 percent, respectively, and discontinuation in 10.5 and 1.1 percent, respectively.

“AEs were generally manageable with supportive care and dose modifications [and] no new safety signals were identified,” said Vergote. He noted that OS data is currently immature with analysis expected in early 2023.

There were no deaths in either group. In terms of patient-reported quality of life outcomes*, no significant differences in global health, physical functioning, or symptoms were documented between the selinexor and placebo arms.

When discussing the study, Dr Kristin Bixel from The Ohio State University and The James Comprehensive Cancer Center, Columbus, Ohio, US, highlighted the influence of histology and molecular subtype on the magnitude of PFS benefit. As such, she queried if the treatment should be tailored to patients according to these criteria to prevent toxicity in patients who may not derive benefit from this regimen.

In addition, multiple trials are ongoing that could potentially bring immunotherapy for endometrial cancer into the frontline setting, changing standard of care. This raises the question on the utility of selinexor moving forward, she said.