Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer
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Published:2023-12-10
Issue:35
Volume:41
Page:5400-5410
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Vergote Ignace1ORCID, Pérez-Fidalgo Jose Alejandro2ORCID, Hamilton Erika Paige3ORCID, Valabrega Giorgio4, Van Gorp Toon1ORCID, Sehouli Jalid5, Cibula David6ORCID, Levy Tally7ORCID, Welch Stephen8, Richardson Debra L.9ORCID, Guerra Eva M.10, Scambia Giovanni11ORCID, Henry Stéphanie12ORCID, Wimberger Pauline13ORCID, Miller David S.14ORCID, Klat Jaroslav15ORCID, Martínez-Garcia Jerónimo16ORCID, Raspagliesi Francesco17, Pothuri Bhavana18ORCID, Romero Ignacio19ORCID, Bergamini Alice2021ORCID, Slomovitz Brian22, Schochter Fabienne23ORCID, Høgdall Estrid24, Fariñas-Madrid Lorena25, Monk Bradley J.26ORCID, Michel Dayana27ORCID, Kauffman Michael G.27, Shacham Sharon27, Mirza Mansoor Raza28ORCID, Makker Vicky29ORCID, Vergote Ignace, Van Gorp Toon, Cadron Isabelle, Barbeaux Annelore, Cornez Nathalie, Henry Stephanie, Kerger Joseph, Debaere Debbie, Denys Hannelore, Mirza Mansoor Raza, Oza Amit, Gilbert Lucy, Welch Stephen, Kolinsky Michael, Zhou Qi, Wang Jing, Yang Yingjie, Tu Kaijia, Wang Li, Wang Danbo, Lou Ge, Yan Xiaojian, Yang Jiaxin, Cibula David, Klat Jaroslav, Melichar Bohuslav, Zikan Michal, Reginacova Klaudia, Weinberger Vit, Sehouli Jalid, Wimberger Pauline, Bauerschlag Dirk, Trillsch Fabian, Tome Oliver, Schochter Fabienne, Battista Marco, Aktas Bahriye, Luebbe Kristina, Deryal Mustafa, Fountzilas George, Christopoulou Athina, Papadimitriou Christos, Zagouri Flora, Helpman Limor, Safra Tamar, Levy Tally, Bruchim Ilan, Rosengarten Ora, Zick Aviad, Valabrega Giorgio, Scambia Giovanni, Mangili Giorgia, Raspagliesi Francesco, Pisano Carmela, Sartori Donata, de Giorgi Ugo, Perez-Fidalgo Jose Alejandro, Gomez-Raposo Cesar, Romero Ignacio, Iglesias Maria, Santaballa Ana, Ancizar Nerea, Estévez Purificación, Maximiano Constanza, Yubero Alfonso, Oaknin Ana, Guerra Eva, Gaba Lydia, Martinez Jeronimo, Dotor Emma, Makker Vicky, Richardson Debra, Berek Jonathan, Chon Hye Sook, Buscema Joseph, Tenney Meaghan, Miller David, Sutton Gregory, Spitz Daniel, LyBarger Kristopher, Hamilton Erika, Gilmore Gregory, Shum Merrill, Amin Harshad, Randall Leslie, Pothuri Bhavana, Robison Katina, Boone Jonathan, Barlin Joyce, Ghamande Sharad, Guirguis Alfred, Sharma Sudarshan, Podzielinski Iwona, Landrum Lisa, Nevadunsky Nicole, Jackson Amanda, Miller Eirwen, Gogoi Radhika, Monk Bradley, Tibayan Restituto, Cloven Noelle, de la Garza Joseph, Lee Christine, Mathews Carolyn, Priebe Anna, Teneriello Michael, Anderson Charles, Pothuri Bhavana, Cappuccini Fabio, Miller David, Kaufman Michael G., Shacham Sharon, Landesman Yosef, Walker Christopher J., Wang Xulong, Wang Feng, Meng Changting, Michel Dayana, Judson Patricia, Rangwala Reshma,
Affiliation:
1. BGOG, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium 2. INCLIVA, CIBERONC, GEICO, Hospital Clinico Universitario de Valencia, Spain 3. Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN 4. MITO and Department of Oncology, University of Torino, Mauriziano Hospital, Turin, Italy 5. Department of Gynecology, NOGGO, European Competence Center for Ovarian Cancer, Charité Comprehensive Cancer Center, Charité–Berlin University of Medicine, Berlin, Germany 6. CEEGOG, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic 7. Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ISGO, Wolfson Medical Center, Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Holon, Israel 8. London Health Sciences Centre, London, ON, Canada 9. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 10. GEICO, Hospital Universitario Ramon y Cajal, Madrid, Spain 11. MITO, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy 12. CHU UCL Namur Site Ste Elisabeth, Service d'onco-hématologie (SORMN), BGOG and Université Catholique de Louvain, Namur, Belgium 13. Department of Obstetrics and Gynecology, University Hospital Carl Gustav Carus, NOGGO and Technische Universitat Dresden, Dresden, Germany 14. Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 15. University Hospital Ostrava and University of Ostrava, Ostrava-Poruba, Czech Republic 16. Department of Oncology, GEICO, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain 17. Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, Italy 18. NYU Langone Health, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 19. Medical Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia, Spain 20. Department of Obstetrics and Gynecology, San Raffaele Milano, Milano, Italy 21. Università Vita-Salute San Raffaele, Milano, Italy 22. Mount Sinai Medical Center, Florida International University, Miami, FL 23. Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany 24. Department of Pathology, Herlev Hospital Copenhagen University Hospital, Copenhagen, Denmark 25. Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Barcelona, Spain 26. GOG, HonorHealth, University of Arizona, Creighton University, Phoenix, AZ 27. Karyopharm Therapeutics, Newton, MA 28. Rigshospitalet—Copenhagen University Hospital, Copenhagen, Denmark 29. Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY
Abstract
PURPOSE 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. PATIENTS AND METHODS 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 ). RESULTS 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%). CONCLUSION 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.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
20 articles.
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