Show simple item record

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.date.accessioned2022-06-24T10:44:55Z
dc.date.available2022-06-24T10:44:55Z
dc.date.issued2022-04-08
dc.identifier.citationJournal of Clinical Oncology, 2022, pp. JCO2101829 -en_US
dc.identifier.issn0732-183X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5194
dc.identifier.eissn1527-7755
dc.identifier.eissn1527-7755
dc.identifier.doi10.1200/JCO.21.01829
dc.identifier.doi10.1200/JCO.21.01829
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: ClinicalTrials.gov 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.formatPrint-Electronic
dc.format.extentJCO2101829 -
dc.languageeng
dc.language.isoengen_US
dc.publisherAmerican Society of Clinical Oncology (ASCO)en_US
dc.relation.ispartofJournal of Clinical Oncology
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleSelinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2033-02-08
dc.date.updated2022-06-24T10:44:10Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1200/JCO.21.01829en_US
rioxxterms.licenseref.startdate2022-04-08
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35394800
pubs.organisational-group/ICR
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


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by-nc-nd/4.0/
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/