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Title: Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial
Author: Gounder, Mrinal M.
Razak, Albiruni Abdul
Somaiah, Neeta
Chawla, Sant
Marti Broto, Javier
Grignani, Giovanni
Schuetze, Scott M.
Vincenzi, Bruno
Wagner, Andrew J.
Chmielowski, Bartosz
Jones, Robin L.
Riedel, Richard F.
Stacchiotti, Silvia
Loggers, Elizabeth T.
Ganjoo, Kristen N.
Le Cesne, Axel
Italiano, Antoine
Garcia Del Muro, Xavier
Burgess, Melissa
Piperno Neumann, Sophie
Ryan, Christopher
Mulcahy, Mary F.
Forscher, Charles
Penel, Nicolas
Okuno, Scott
Elias, Anthony
Hartner, Lee
Philip, Tony
Alcindor, Thierry
Kasper, Bernd
Reichardt, Peter
Lapeire, Lore
Blay, Jean Yves
Chevreau, Christine
Valverde Morales, Claudia Maria
Schwartz, Gary K.
Chen, James L.
Deshpande, Hari
Davis, Elizabeth J.
Nicholas, Garth
Gröschel, Stefan
Hatcher, Helen
Duffaud, Florence
Herráez, Antonio Casado
Beveridge, Roberto Diaz
Badalamenti, Giuseppe
Eriksson, Mikael
Meyer, Christian
Von Mehren, Margaret
Van Tine, Brian A.
Götze, Katharina
Mazzeo, Filomena
Yakobson, Alexander
Zick, Aviad
Lee, Alexander
Gonzalez, Anna Estival
Napolitano, Andrea
Dickson, Mark A.
Michel, Dayana
Meng, Changting
Li, Lingling
Liu, Jianjun
Ben Shahar, Osnat
Van Domelen, Dane R.
Walker, Christopher J.
Chang, Hua
Landesman, Yosef
Shah, Jatin J.
Shacham, Sharon
Kauffman, Michael G.
Attia, Steven
Keywords: Sarcoma
Placebos (Medicine)
Issue Date: 1-Aug-2022
Publisher: American Society of Clinical Oncology (ASCO)
Abstract: PURPOSE Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis ( identifier: ). RESULTS Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted. (C) 2022 by American Society of Clinical Oncology
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It is part of: Journal of Clinical Oncology, 2022, vol. 40, num. 22, p. 2479-2490
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ISSN: 1527-7755
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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