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

2023; Lippincott Williams & Wilkins; Volume: 41; Issue: 35 Linguagem: Inglês

10.1200/jco.22.02906

1527-7755

Ignace Vergote, José Alejandro Pérez Fidalgo, Erika Hamilton, Giorgio Valabrega, Toon Van Gorp, Jalid Sehouli, David Cibula, Tally Levy, Stephen Welch, Debra L. Richardson, Eva Guerra, Giovanni Scambia, Stéphanie Henry, Pauline Wimberger, David S. Miller, Jaroslav Klát, Jerónimo Martínez, Francesco Raspagliesi, Bhavana Pothuri, Ignacio Romero, Alice Bergamini, Brian M. Slomovitz, Fabienne Schochter, Estrid Høgdall, Lorena Fariñas-Madrid, Bradley J. Monk, Dayana Michel, Michael Kauffman, Sharon Shacham, Mansoor Raza Mirza, Vicky Makker, Ignace Vergote, Toon Van Gorp, Isabelle Cadron, Annelore Barbeaux, Nathalie Cornez, Stéphanie Henry, Joseph Kerger, Debbie Debaere, Hannelore Denys, Mansoor Raza Mirza, Amit M. Oza, Lucy Gilbert, Stephen Welch, Michael Kolinsky, Qi Zhou, Jing Wang, Yingjie Yang, Kaijia Tu, Li Wang, Danbo Wang, Ge Lou, Xiaojian Yan, Jiaxin Yang, David Cibula, Jaroslav Klát, Bohuslav Melichar, Michal Zikán, Klaudia Reginacova, Vít Weinberger, Jalid Sehouli, Pauline Wimberger, Dirk Bauerschlag, Fabian Trillsch, Oliver Tomé, Fabienne Schochter, Marco Johannes Battista, Bahriye Aktas, Kristina Luebbe, Mustafa Deryal, George Fountzilas, Athina Christopoulou, Christos Papadimitriou, Flora Zagouri, Limor Helpman, Tamar Safra, Tally Levy, Ilan Bruchim, Ora Rosengarten, Aviad Zick, Giorgio Valabrega, Giovanni Scambia, Giorgia Mangili, Francesco Raspagliesi, Carmela Pisano, Donata Sartori, Ugo De Giorgi, José Alejandro Pérez Fidalgo, César Gómez Raposo, Ignacio Romero, María Iglesias, Ana Santaballa, N. Ancizar, Purificación Estévez, Constanza Maximiano, A. Yubero, Ana Oaknin, Eva Guerra, Lydia Gaba, Jerónimo Martínez, E. Dotor, Vicky Makker, Debra L. Richardson, Jonathan S. Berek, Hye Sook Chon, Joseph Buscema, Meaghan Tenney, David S. Miller, Gregory P. Sutton, Daniel L. Spitz, Kristopher LyBarger, Erika Hamilton, Gregory Gilmore, M. Shum, Harshad Amin, Leslie M. Randall, Bhavana Pothuri, Katina Robison, Jonathan Boone, Joyce N. Barlin, Sharad Ghamande, Alfred Guirguis, Sudarshan Sharma, Iwona Podzielinski, Lisa M. Landrum, Nicole Nevadunsky, Amanda Jackson, Eirwen M. Miller, Radhika Gogoi, Bradley J. Monk, Restituto Tibayan, Noelle Cloven, Joseph de la Garza, Christine Lee, Carolyn Mathews, Anna Priebe, Michael Teneriello, Charles Anderson, Bhavana Pothuri, Fabio Cappuccini, David S. Miller, Michael G. Kaufman, Sharon Shacham, Yosef Landesman, Christopher J. Walker, Xulong Wang, Feng Wang, Changting Meng, Dayana Michel, Patricia L. Judson, Reshma Rangwala,

Sarcoma Diagnosis and Treatment

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.