Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer
Authors: Vergote Ignace , Pérez-Fidalgo Jose Alejandro , Hamilton Erika Paige , Valabrega Giorgio , Van Gorp Toon , Sehouli Jalid , Cibula David , Levy Tally , Welch Stephen , Richardson Debra L. , Guerra Eva M. , Scambia Giovanni , Henry Stéphanie , Wimberger Pauline , Miller David S. , Klat Jaroslav , Martínez-Garcia Jerónimo , Raspagliesi Francesco , Pothuri Bhavana , Romero Ignacio , Bergamini Alice , Slomovitz Brian , Schochter Fabienne , Høgdall Estrid , Fariñas-Madrid Lorena , Monk Bradley J. , Michel Dayana , Kauffman Michael G. , Shacham Sharon , Mirza Mansoor Raza , Makker Vicky ,   on behalf of the ENGOT-EN5/GOG-3055/SIENDO Investigators, 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 
Published: September 2023

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.