Selinexor Maintenance Therapy Demonstrated Durable PFS Benefit Among Patients With Advanced or Recurrent TP53 Wild-Type Endometrial Cancer

According to long-term follow-up results from a pre-specified subgroup of patients with wild type TP53 (TP53wt) endometrial cancer in the double-blinded phase 3 SIENDO trial, maintenance therapy with selinexor, an investigational oral XPO1 inhibitor, prior to systemic therapy showed a durable progression-free survival (PFS) benefit among patients. 

These findings were presented at the 2023 American Society of Clinical Oncology (ASCO) Plenary by Brian Slomovitz, MD, Mount Sinai Medical Center, Miami Beach, Florida.

In this subgroup of the SIENDO trial, 113 patients with advanced or recurrent TP53wt disease were randomized to receive either selinexor (n = 77) or placebo (n = 36) in the maintenance line prior to systemic therapy for safety and efficacy end points. Preliminary analysis of this exploratory subgroup, as previously reported, "showed a decrease in risk for progression or death with a median PFS of 13.7 months with selinexor as maintenance therapy vs 3.7 months with placebo,” wrote Dr Slomovitz and coauthors.

At the data cutoff date for this long-term analysis of November 30th, 2022, median follow-up was 20.3 months. At that time the percentage of patients who continued treatment in the selinexor arm was 26.3% compared with 22.9% in the placebo arm. Median PFS was 20.8 months in the selinexor arm and 5.2 months in the placebo arm (hazard ratio [HR; stratified by chemotherapy response CR vs PR] 0.46; 95% confidence interval [CI], 0.27 to 0.79; nominal one-sided P = .002). 

The most common adverse events of any grade included nausea, vomiting, and diarrhea. The most common grade ≥3 adverse events included neutropenia, nausea, and thrombocytopenia. Treatment-related adverse events that led to treatment discontinuation were experienced by 15% of patients in the selinexor arm and 0% of patients in the placebo arm. 

“These data suggest that TP53 status is a robust prognostic biomarker for [endometrial cancer] and selinexor may provide meaningful benefit in patients who have TP53wt tumors,” concluded Dr Slomovitz and coauthors. Kathleen N. Moore, MD, Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, Oklahoma, commented, “Should these findings be confirmed in a definitive phase 3 study, it will give patients with TP53 wild-type tumors a new approach for preventing recurrence.” 

A phase 3 study is currently being conducted to further investigate the safety and efficacy of selinexor in the maintenance line in this patient population. 

Source: 

Maintenance therapy with selinexor may extend progression-free survival for some endometrial cancer patients. News release. ASCO; July 24, 2023. https://old-prod.asco.org/about-asco/press-center/news-releases/maintenance-therapy-selinexor-may-extend-progression-free

Slomovitz B, Perez-Fidalgo JA, Hamilton EP, et al. Long-term follow up of selinexor maintenance in patients with TP53wt advanced or recurrent endometrial cancer: A pre-specified subgroup analysis from the phase 3 ENGOT-EN5/GOG-3055/SIENDO study. Presented at 2023 ASCO Plenary Series; July 25, 2023; virtual. Abstract 427956