Dr Miller on the Efficacy of Selinexor in TP53 Wild-Type Endometrial Cancer

David S. Miller, MD, professor, Department of Obstetrics and Gynecology, Dallas Foundation Chair in Gynecologic Oncology, Amy and Vernon E. Faulconer Distinguished Chair in Medical Science, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, discusses the efficacy of treatment with selinexor (Xpovio) in patients with advanced or recurrent TP53 wild-type endometrial cancer based on updated data from the exploratory subgroup analyses of the phase 3 SIENDO study (NCT03555422).

These prespecified subgroups analyses evaluated the long-term efficacy and safety of selinexor maintenance, Miller begins. Findings were initially presented at the 2024 ASCO Annual Meeting, with longer-term follow-up data subsequently reported at the International Gynecologic Cancer Society 2024 Annual Global Meeting.

In this recent analysis which evaluated patients according to mismatch repair status, selinexor significantly extended progression-free survival (PFS) compared with placebo in patients with TP53 wild-type, mismatch repair–proficient (pMMR) disease, Miller reports. After a median follow-up of 38.5 months, patients receiving selinexor (n = 47) achieved a median PFS of 39.5 months (95% CI, 19.3-not reached [NR]) vs 4.9 months (95% CI, 2.0-NR) with placebo (n = 23; HR, 0.36; 95% CI, 0.19-0.71; one-sided nominal P= .0011). However, this improvement was less pronounced in patients with mismatch repair–deficient (dMMR) disease, who typically respond well to immune therapy, he notes. Among patients with dMMR, TP53 wild-type disease (n = 29), selinexor (n = 20) produced a median PFS of 13.1 months (95% CI, 3.6-NR) vs 3.7 months (95% CI, 1.9-NR) with placebo (n = 9) following 32.8 months of median follow-up (HR, 0.49; 95% CI, 0.18-1.34; one-sided nominal P = .0825).

Although overall survival (OS) data in the TP53 wild-type subgroup remain immature, preliminary results show a trend in favor of selinexor (HR, 0.65); median OS has not yet been reached, Miller adds.

Additionally, an analysis of quality-adjusted time without symptoms or toxicity demonstrated a meaningful increase in quality- and toxicity-adjusted PFS with selinexor, showing a difference of 10.63 months compared with placebo. For the TP53 wild-type, pMMR group, selinexor conferred a PFS benefit of 12.70 months relative to placebo. These data suggest that selinexor may be particularly beneficial for patients with TP53 wild-type, pMMR disease, providing extended disease control and improved quality of life, Miller concludes.