Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer

Author(s): Ignace Vergote, MD1; Jose Alejandro Pérez-Fidalgo, MD2; Erika Paige Hamilton, MD3; Giorgio Valabrega, MD4; Toon Van Gorp, MD1; Jalid Sehouli, MD5; David Cibula, MD6; Tally Levy, MD7; Stephen Welch, MD8; Debra L. Richardson, MD9; Eva M. Guerra, MD10; Giovanni Scambia, MD11; Stéphanie Henry, MD12; Pauline Wimberger, MD13; David S. Miller, MD14; Jaroslav Klat, MD15; Jerónimo Martínez-Garcia, MD16; Francesco Raspagliesi, MD17; Bhavana Pothuri, MD18; Ignacio Romero, MD19; Alice Bergamini, MD20,21; Brian Slomovitz, MD22; Fabienne Schochter, MD23; Estrid Høgdall, MD24; Lorena Fariñas-Madrid, MD25; Bradley J. Monk, MD26; Dayana Michel, MD27; Michael G. Kauffman, MD28; Sharon Shacham, PhD28; Mansoor Raza Mirza, MD29; Vicky Makker, MD30
Source: https://doi.org/10.1200/JCO.22.02906
Maem Hussein MD

Dr. Maen Hussein's Thoughts

This is another possibility for maintenance therapy. It will require further study.


Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer (EC). The primary end point was to assess progression-free survival (PFS) with once-weekly oral selinexor in patients with advanced or recurrent EC.


ENGOT-EN5/GOG-3055/SIENDO was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III study at 107 sites in 10 countries. Patients 18 years or older with histologically confirmed EC were enrolled. All had completed a single line of at least 12 weeks of taxane-platinum combination chemotherapy and achieved partial or complete response. Patients were assigned to receive 80 mg oral selinexor once weekly or placebo with 2:1 random assignment (ClinicalTrials.gov identifier: NCT03555422).


Between January 2018 and December 2021, 263 patients were randomly assigned, with 174 allocated to selinexor and 89 to placebo. The median PFS was 5.7 months (95% CI, 3.81 to 9.20) with selinexor versus 3.8 months (95% CI, 3.68 to 7.39) with placebo (hazard ratio [HR], 0.76 [95% CI, 0.54 to 1.08]; two-sided P = .126), which did not meet the criteria for statistical significance in the intent-to-treat population. Incorrect chemotherapy response stratification data for 7 (2.7%) patients were identified. In a prespecified exploratory analysis of PFS in audited stratification data, PFS for selinexor met the threshold for statistical significance (HR, 0.71; 95% CI, 0.499 to 0.996; two-sided P = .049). Furthermore, patients with the TP53 wild-type (wt) EC had a median PFS of 13.7 and 3.7 months with selinexor and placebo. The most common grade 3 treatment-related adverse events were nausea (9%), neutropenia (9%), and thrombocytopenia (7%).


The significance level for PFS was only met in the audited analysis. However, a preliminary analysis of a prespecified exploratory subgroup of patients with TP53wt EC showed promising results with selinexor maintenance therapy.

Author Affiliations

1BGOG, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; 2INCLIVA, CIBERONC, GEICO, Hospital Clinico Universitario de Valencia, Spain; 3Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; 4MITO and Department of Oncology, University of Torino, Mauriziano Hospital, Turin, Italy; 5Department of Gynecology, NOGGO, European Competence Center for Ovarian Cancer, Charité Comprehensive Cancer Center, Charité–Berlin University of Medicine, Berlin, Germany; 6CEEGOG, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; 7Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ISGO, Wolfson Medical Center, Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Holon, Israel; 8London Health Sciences Centre, London, ON, Canada; 9Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK; 10GEICO, Hospital Universitario Ramon y Cajal, Madrid, Spain; 11MITO, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 12CHU UCL Namur Site Ste Elisabeth, Service d’onco-hématologie (SORMN), BGOG and Université Catholique de Louvain, Namur, Belgium; 13Department of Obstetrics and Gynecology, University Hospital Carl Gustav Carus, NOGGO and Technische Universitat Dresden, Dresden, Germany; 14Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; 15University Hospital Ostrava and University of Ostrava, Ostrava-Poruba, Czech Republic; 16Department of Oncology, GEICO, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain; 17Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, Italy; 18NYU Langone Health, Perlmutter Cancer Center, New York University School of Medicine, New York, NY; 19Medical Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia, Spain; 20Department of Obstetrics and Gynecology, San Raffaele Milano, Milano, Italy; 21Università Vita-Salute San Raffaele, Milano, Italy; 22Mount Sinai Medical Center, Florida International University, Miami, FL; 23Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany; 24Department of Pathology, Herlev Hospital Copenhagen University Hospital, Copenhagen, Denmark; 25Gynaecologic Cancer Programme, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Barcelona, Spain; 26GOG, HonorHealth, University of Arizona, Creighton University, Phoenix, AZ; 27Karyopharm Therapeutics, Newton, MA; 28Karyopharm Therapeutics, Newton, MA; 29Rigshospitalet—Copenhagen University Hospital, Copenhagen, Denmark; 30Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY

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