Long-term follow-up of selinexor maintenance therapy in patients with p53 wild-type endometrial cancer has demonstrated anticancer activity, according to data presented by Brian M. Slomovitz, MD, and colleagues during the ASCO Plenary Series: July 2023 Session (Abstract 427956). Results of the phase III ENGOT-EN5/GOG-3055/SIENDO study showed a substantial increase in progression-free survival among patients in the p53 wild-type subgroup receiving selinexor, with a median progression-free survival of 27.4 months vs 5.2 months among those receiving placebo (hazard ratio [HR] = 0.42).

Based on these findings, the study authors underscored the potential opportunity for more personalized therapies in this challenging patient population.

Brian M. Slomovitz, MD

“These results provide strong rationale to further evaluate selinexor as maintenance therapy in p53 wild-type endometrial cancers, a unique patient population with a high unmet need,” said Dr. Slomovitz, Director of Gynecologic Oncology at Mount Sinai Medical Center, Miami Beach, Florida. “p53 status may serve as a robust predictive biomarker for efficacy in endometrial cancers, potentially enabling more personalized therapies in the maintenance setting.”

As Dr. Slomovitz explained, endometrial cancer treatment has seen rapid advancements, with molecular characterizations such as microsatellite instability status now helping to guide treatment plans. Immune checkpoint inhibitors have shown a significant benefit in patients with microsatellite instability or mismatch repair–deficient tumors, he said. However, there remains a high, unmet need for patients with microsatellite-stable or mismatch repair–proficient disease, particularly those with p53 wild-type tumors, which constitute approximately 50% of patients with advanced or recurrent endometrial cancer.

The SIENDO trial is a randomized, double-blind, phase III trial evaluating selinexor as maintenance treatment in patients with stage IV disease or a first relapse of endometrial cancer. After receiving 12 weeks of platinum-based chemotherapy and achieving either a complete or partial response, patients were randomly assigned 2:1 to receive once-weekly oral selinexor or placebo. The primary endpoint was investigator-assessed progression-free survival, with exploratory endpoints including histologic subtype and molecular subclassifications.

Improved Progression-Free Survival in p53 Wild-Type Patients

Results from the trial showed that patients with p53 wild-type tumors receiving selinexor maintenance therapy had a median progression-free survival of 27.4 months compared with 5.2 months in the placebo group, representing a 58% decrease in the risk of disease progression (HR = 0.42). As Dr. Slomovitz reported, the benefit was isolated to patients with p53 wild-type disease, indicating this may be a robust biomarker for identifying patients who may respond to selinexor therapy.

A further analysis revealed that progression-free survival improvements were observed in p53 wild-type patients regardless of their microsatellite instability status, with the most significant benefit seen in the p53 wild-type mismatch repair–proficient group. In this subgroup, median progression-free survival was not reached after 27 months for those receiving selinexor compared with 4.9 months among those receiving placebo, representing a 68% decrease in the risk of disease progression.

Selinexor's safety profile was generally manageable, said Dr. Slomovitz, with the most commonly reported treatment-emergent adverse events being nausea, vomiting, and diarrhea. Rare cases of grade ≥ 3 adverse events included neutropenia, thrombocytopenia, and nausea. There was one grade 4 adverse event reported—a colonic abscess—which occurred in the placebo arm. The incidence and severity of adverse events were also similar in the p53-mutated group. About 16% of patients discontinued selinexor because of adverse events.

Ongoing research, including the XPORT-EC-042 trial (ClinicalTrials.gov identifier NCT05611931), will further evaluate selinexor as maintenance therapy in patients with endometrial cancer.

Disclosure: For full disclosures of the study authors, visit meetings.asco.org.