Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2024

Longer-term Safety and Efficacy of Selinexor Maintenance Therapy for Patients With TP53wt Advanced or Recurrent Endometrial Cancer: Follow-up Subgroup Analysis of the ENGOT-EN5/GOG-3055/SIENDO Study (#246)

Paul Haluska 1 , Jose Alejandro Pérez-Fidalgo 2 , Ignace Vergote 3 , Erika Hamilton 4 , Ugo de Giorgi 5 , Toon Van Gorp 3 , Kristina Lübbe 6 , Michael Zikan 7 , Limor Helpman 8 , David S. Miller 9 , Lorena Fariñas-Madrid 10 , Carmela Pisano 11 , Annelore Barbeaux 12 , Jalid Sehouli 13 , Hye Sook Chon 14 , Nerea Ancizar 15 , Jonathan Berek 16 , Pratheek Kalyanapu 1 , Mansoor Raza Mirza 1 , Vicky Makker 17
  1. Karyopharm Therapeutics, Newtown, MA, United States
  2. GEICO and Hospital Clinico Universitario de Valencia, INCLIVA, CIBERONC, Valencia, Spain
  3. Belgium and Luxembourg Gynaecological Oncology Group, Leuven Cancer Institute, University Hospitals, Leuven, Belgium
  4. Sarah Cannon Research Institute, Nashville, TN, USA
  5. IRCCS Istituto Romagnolo per lo Studio dei Tumori IRST, Meldola, Italy
  6. DIAKOVERE Henriettenstift Gynäkologie, Hannover, Germany
  7. Department of Gynecology and Obstetrics, Charles University - First Faculty of Medicine and University Hospital, Bulovka, Czech Republic
  8. Department of Gynecological Oncology, Sheba Medical Center, Tel-Hashomer, Israel
  9. Department of Obstetrics and Gynecology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, USA
  10. Vall d’Hebron Universitiy Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain
  11. Istituto Nazionale Tumori di Napoli, Naples, Italy
  12. CHR , Verviers, Belgium
  13. NOGGO and Department of Gynecology, European Competence Center for Ovarian Cancer, Charité Comprehensive Cancer Center, Charité–Berlin University of Medicine, Berlin, Germany
  14. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fl, USA
  15. GEICO andHospital Universitario de Donostia, Donostia, Spain
  16. Stanford Women’s Cancer Center, Stanford Cancer Institute, University School of Medicine, Stanford, CA, USA
  17. Memorial Sloan Kettering Cancer Center, NYC, NY, USA

Background: Molecular characterization is important to inform treatment decisions for endometrial cancer (EC). Wild type TP53 (TP53wt) is found in ≥50% of advanced or recurrent EC; of those cases, 60%–78% are also categorized as proficient mismatch repair (pMMR). Evidence of benefit for these molecular subgroups is limited for patients with TP53wt tumors.

Methods: This was a long-term follow-up analysis of the prespecified TP53wt exploratory subgroup of ENGOT-EN5/GOG-3055/SIENDO (NCT03555422), a randomized, double-blind, phase 3 trial evaluating selinexor versus placebo as maintenance treatment for advanced or recurrent EC following response to prior systemic therapy.

Results: A total of 113 patients with TP53wt EC were randomized to selinexor (n=77) or placebo (n=36) as maintenance therapy. Median follow-up was 36.8 months; 15 patients remained on treatment as of April 1, 2024. Median progression-free survival (mPFS) was 28.4 months with selinexor versus 5.2 months with placebo (HR: 0.44; 95% CI [0.27–0.73], nominal one-sided p=0.0005). PFS improvement was observed regardless of mismatch repair status; respective mPFS was 39.5 months versus 4.9 months in the TP53wt/proficient mismatch repair (pMMR) subgroup and 13.1 months versus 3.7 months in the TP53wt/deficient mismatch repair (dMMR) subgroup. Any-grade treatment-emergent adverse events (TEAEs) occurred in 99% and 94% of patients in the selinexor and placebo arms, respectively. The most common TEAEs were nausea (selinexor/placebo: 89%/40%), vomiting (61%/14%), and diarrhea (45%/37%); 17% of patients discontinued selinexor due to TEAEs. One death occurred in the placebo group.

Conclusions: TP53wt status may represent a robust predictive biomarker for selinexor efficacy in EC. A strong PFS signal was observed regardless of mismatch repair status, particularly in the TP53wt/pMMR subgroup, a patient population with high unmet need.