Maintenance Selinexor Shows PFS in TP53 Wild-type Endometrial Cancer


Significant progression-free survival was seen in those with TP53 wild-type advanced/recurrent endometrial cancer who were treated with maintenance selinexor.

Selinexor did not show a clinically meaningful improvement in the general study population.

Selinexor did not show a clinically meaningful improvement in the general study population.

Maintenance selinexor (Xpovio) showed a significant progression-free survival (PFS) benefit compared with placebo in a subgroup of patients with TP53 wild-type advanced/recurrent endometrial cancer, according to findings from the phase 3 ENGOT-EN5/GOG-3055/SIENDO trial (NCT03555422).1,2

Data from the trial, which were presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS), indicated a median PFS of 27.4 months (95% CI, 13.1-not reached [NR]) with selinexor compared with 5.2 months (95% CI, 2.0-13.1) in the placebo arm in those with TP53 wild-type disease (HR, 0.41; 95% CI, 0.25-0.69; one-sided P = .0002).

Selinexor did not show a clinically meaningful improvement in the general study population.

“The safety profile for selinexor was generally manageable and we know that the TP53 wild-type status may represent a robust predictive biomarker for selinexor efficacy [in endometrial cancer],” lead author Giovanni Scambia, MD, chair of the Department of Health Science and Public Health of Universita Cattolica del Sacro Cuore, Italy, said in a presentation during the meeting. “These results highlight the potential opportunity to further personalize therapies and provide a strong rationale to further evaluate selinexor as a maintenance therapy.” 

The randomized, double-bind, phase 3 trial included 263 patients with stage IV or first relapsed endometrial cancer. Patients must have received at least 12 weeks of platinum-based chemotherapy and must have shown a partial response (PR) or complete response (CR) to first-line chemotherapy. Prior surgery, radiation, or hormone therapy was permitted.

Patients were randomized 2:1 to receive either oral 80 mg of selinexor or placebo weekly. Patients were stratified based on cancer stage (primary stage IV vs recurrent) and response (complete vs partial).

In the arms receiving selinexor and placebo, respectfully, 97.4% and 94.4% were white. The median age was 64 years old (40-81) for the selinexor arm and 61.5 years (33-74) for the placebo arm. More than 80% of patients in both groups had endometrioid cancer. In the selinexor arm, 44.2% of patients had primary stage IV disease at time of therapy, and 53.2% had recurrent disease. In the placebo arm, 47.2% had primary stage IV disease, and 50.0% had recurrent disease.

The primary end point for this study was investigator-assessed PFS. Secondary end points included overall survival (OS) and time to first subsequent therapy (TFST). Select exploratory end points included histological subtype and molecular subclassification assessed by DNA sequencing and immunohistochemistry (IHC), specifically regarding TP53 mutation status, microsatellite instability status, and POLE-EDM.

In those with microsatellite stable (MSS)/mismatch repair proficient (pMMR) disease, the median PFS with selinexor was not reached (95% CI, 19.3-NR) compared with 4.9 months (95% CI, 2.0-NR) with placebo (HR, 0.32; 95% CI, 0.16-0.64; one-sided P = .0004). Median PFS in those with microsatellite instability–high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer was 13.1 months (95% CI, 3.6-NR) vs 3.7 months (95% CI, 1.9-NR) with selinexor and placebo, respectively (HR, 0.45; 95% CI, 0.16-1.27; one-sided P = .0643).

Preliminary OS in those with TP53 wild-type showed no response (NR) with selinexor (NR, NR) or with placebo (35.19, NR; HR, 0.76; 95% CI, 0.36-1.59; one-sided P = .24) with a median follow up of 28.9 months. Preliminary OS in those with TP53 wild-type/pMMR showed NR with selinexor (NR, NR) and 35.19 months with placebo (28.68, NR; HR, 0.57; 95% CI, 0.24-1.35; one-sided P = .098) with a median follow up of 31.6 months. In those with TP53 wild-type/dMMR, there was no response with either treatment (HR, 0.62; 95% CI, 0.06-6.81; one-sided P = .35).

In terms of treatment-emergent adverse events (TEAEs) in patients with TP53 wild-type, any-grade toxicities in the selinexor and placebo groups, respectively, included nausea (90% vs 34%), vomiting (60% vs 11%), diarrhea (42% vs 37%), constipation (33% vs 40%), and asthenia (36% vs 26%). Grade 3/4 TEAEs in the selinexor arm included neutropenia (18%), nausea (12%), thrombocytopenia (10%), and fatigue (8%). In the placebo arm, these grade 3/4 TEAEs were constipation (6%), abdominal pain (3%), and vomiting (3%).

TEAEs resulted in discontinuation of treatment in 16% of the selinexor arm and none in the control arm.

Currently, selinexor is being assessed as maintenance therapy after systematic therapy for patients with p53 wild-type, advanced or recurrent endometrial carcinoma in the ongoing ENGOT-EN20/GOG-3083/ XPORT-EC-042 (NCT05611931).3


  1. Scambia G, Vergote I, Hamilton E, et al. Selinexor maintenance for patients with TP53wt advanced or recurrent endometrial cancer: long-term follow up of efficacy and safety subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study. Presented at: 2023 Annual Global Meeting of the International Gynecologic Cancer Society; November 5-7, 2023; Seoul, Korea.
  2. Vergote I, Pérez-Fidalgo JA, Hamilton EP, et al. Oral selinexor as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer. J Clin Oncol. Published online September 5, 2023. doi:10.1200/jco.22.02906
  3. Vergote I, Mirza MR, Coleman RL, et al. ENGOT-EN20/GOG-3083/xport-EC-042: A phase 3, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with P53 wild-type, advanced or recurrent endometrial carcinoma. J Clin Oncol. 2023;41(16_suppl):TPS5627-TPS5627. doi:10.1200/jco.2023.41.16_suppl.tps5627
Related Videos
Considering cystectomy in patients with bladder cancer may help with managing the shortage of Bacillus Calmette-Guerin, according to Joshua J. Meeks, MD, PhD, BS.
Anemia in patients who receive talazoparib plus enzalutamide for metastatic castration-resistant prostate cancer appears to be manageable without any compromises in patient-reported outcomes and quality of life.
Patients with locally advanced or metastatic urothelial cancer and visceral disease may particularly benefit from enfortumab vedotin plus pembrolizumab, according to Amanda Nizam, MD.
High-grade adverse effects with zanidatamab plus palbociclib and fulvestrant seem to be uncommon in patients with HER2-positive, hormone receptor–positive, metastatic breast cancer, according to Sara Hurvitz, MD, FACP.
Black male patients with breast cancer appear to experience worse survival outcomes compared with White patients when controlling for clinicopathological variables, according to Jason (Jincong) Q. Freeman, MPH, MS.
Results from the ECOG-ACRIN E4112 trial appear to support the use of DCIS scores for identifying patients with breast cancer who may be eligible to omit radiotherapy following MRI-guided surgery.
Providers should inform patients with breast cancer that selecting later-line therapies following prior treatment with CDK4/6 inhibitors is a “developing area,” says Abigail M. Johnston, JD.
Data from the phase 3 NATALEE trial highlight a positive toxicity profile for ribociclib as an adjuvant therapy for patients with hormone receptor–positive, HER2-negative breast cancer, says Neil M. Iyengar, MD.
Future research will focus on ctDNA dynamics change over time in the full translational cohort of patients with hormone receptor–positive breast cancer in the phase 3 monarchE study, says Stephanie L. Graff, MD.
Findings from a National Cancer Database analysis highlight no statistically significant differences in survival outcomes with chemotherapy for patients over 81 years old with triple-negative breast cancer compared with those who do not receive chemotherapy.
Related Content