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dc.contributor.authorGounder, MM
dc.contributor.authorRazak, AA
dc.contributor.authorSomaiah, N
dc.contributor.authorChawla, S
dc.contributor.authorMartin-Broto, J
dc.contributor.authorGrignani, G
dc.contributor.authorSchuetze, SM
dc.contributor.authorVincenzi, B
dc.contributor.authorWagner, AJ
dc.contributor.authorChmielowski, B
dc.contributor.authorJones, RL
dc.contributor.authorRiedel, RF
dc.contributor.authorStacchiotti, S
dc.contributor.authorLoggers, ET
dc.contributor.authorGanjoo, KN
dc.contributor.authorLe Cesne, A
dc.contributor.authorItaliano, A
dc.contributor.authorGarcia Del Muro, X
dc.contributor.authorBurgess, M
dc.contributor.authorPiperno-Neumann, S
dc.contributor.authorRyan, C
dc.contributor.authorMulcahy, MF
dc.contributor.authorForscher, C
dc.contributor.authorPenel, N
dc.contributor.authorOkuno, S
dc.contributor.authorElias, A
dc.contributor.authorHartner, L
dc.contributor.authorPhilip, T
dc.contributor.authorAlcindor, T
dc.contributor.authorKasper, B
dc.contributor.authorReichardt, P
dc.contributor.authorLapeire, L
dc.contributor.authorBlay, J-Y
dc.contributor.authorChevreau, C
dc.contributor.authorValverde Morales, CM
dc.contributor.authorSchwartz, GK
dc.contributor.authorChen, JL
dc.contributor.authorDeshpande, H
dc.contributor.authorDavis, EJ
dc.contributor.authorNicholas, G
dc.contributor.authorGröschel, S
dc.contributor.authorHatcher, H
dc.contributor.authorDuffaud, F
dc.contributor.authorHerráez, AC
dc.contributor.authorBeveridge, RD
dc.contributor.authorBadalamenti, G
dc.contributor.authorEriksson, M
dc.contributor.authorMeyer, C
dc.contributor.authorvon Mehren, M
dc.contributor.authorVan Tine, BA
dc.contributor.authorGötze, K
dc.contributor.authorMazzeo, F
dc.contributor.authorYakobson, A
dc.contributor.authorZick, A
dc.contributor.authorLee, A
dc.contributor.authorGonzalez, AE
dc.contributor.authorNapolitano, A
dc.contributor.authorDickson, MA
dc.contributor.authorMichel, D
dc.contributor.authorMeng, C
dc.contributor.authorLi, L
dc.contributor.authorLiu, J
dc.contributor.authorBen-Shahar, O
dc.contributor.authorVan Domelen, DR
dc.contributor.authorWalker, CJ
dc.contributor.authorChang, H
dc.contributor.authorLandesman, Y
dc.contributor.authorShah, JJ
dc.contributor.authorShacham, S
dc.contributor.authorKauffman, MG
dc.contributor.authorAttia, S
dc.coverage.spatialUnited States
dc.identifier.citationJournal of Clinical Oncology, 2022, pp. JCO2101829 -en_US
dc.description.abstractPURPOSE: 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. (Registration: identifier: NCT02606461.). 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.
dc.format.extentJCO2101829 -
dc.publisherAmerican Society of Clinical Oncology (ASCO)en_US
dc.relation.ispartofJournal of Clinical Oncology
dc.titleSelinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)/Sarcoma Clinical Trials (R Jones) (hon.)
pubs.publication-statusPublished online
dc.contributor.icrauthorJones, Robin

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