Afficher la notice abrégée

Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial

dc.rights.licenseopenen_US
dc.contributor.authorITALIANO, Antoine
dc.contributor.authorMIR, Olivier
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMATHOULIN-PELISSIER, Simone
dc.contributor.authorPENEL, Nicolas
dc.contributor.authorPIPERNO-NEUMANN, Sophie
dc.contributor.authorBOMPAS, Emmanuelle
dc.contributor.authorCHEVREAU, Christine
dc.contributor.authorDUFFAUD, Florence
dc.contributor.authorENTZ-WERLE, Natacha
dc.contributor.authorSAADA, Esma
dc.contributor.authorRAY-COQUARD, Isabelle
dc.contributor.authorLERVAT, Cyril
dc.contributor.authorGASPAR, Nathalie
dc.contributor.authorMAREC-BERARD, Perrine
dc.contributor.authorPACQUEMENT, Helene
dc.contributor.authorWRIGHT, John
dc.contributor.authorTOULMONDE, Maud
dc.contributor.authorBESSEDE, Alban
dc.contributor.authorCROMBE, Amandine
dc.contributor.authorKIND, Michele
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBELLERA, Carine
dc.contributor.authorBLAY, Jean Yves
dc.date.accessioned2021-01-27T08:57:36Z
dc.date.available2021-01-27T08:57:36Z
dc.date.issued2020
dc.identifier.issn1474-5488 (Electronic) 1470-2045 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26044
dc.description.abstractEnBackground Patients with Ewing sarcoma or osteosarcoma have a median overall survival of less than 12 months after diagnosis, and a standard treatment strategy has not yet been established. Pharmacological inhibition of MET signalling and aberrant angiogenesis has shown promising results in several preclinical models of Ewing sarcoma and osteosarcoma. We aimed to investigate the activity of cabozantinib, an inhibitor of MET and VEGFR2, in patients with advanced Ewing sarcoma and osteosarcoma. Methods We did a multicentre, single-arm, two-stage, phase 2 trial in patients with advanced Ewing sarcoma or osteosarcoma recruited from ten centres in the French Sarcoma Group. Key eligibility criteria were aged 12 years or older, Eastern Cooperative Oncology Group performance status of 0–1, and documented disease progression (according to Response Evaluation Criteria in Solid Tumors version 1.1) before study entry. The number of previous lines of treatment was not limited. Patients received cabozantinib (adults 60 mg, children [<16 years] 40 mg/m2) orally once daily in 28-day cycles until disease progression, unacceptable toxicity, the investigator's decision to discontinue, or participant withdrawal. The primary endpoint for Ewing sarcoma was best objective response within 6 months of treatment onset; for osteosarcoma, a dual primary endpoint of 6-month objective response and 6-month non-progression was assessed. All enrolled patients who received at least one dose of cabozantinib were included in the safety analysis, and all participants who received at least one complete or two incomplete treatment cycles were included in the efficacy population. This study was registered with ClinicalTrials.gov, number NCT02243605. Findings Between April 16, 2015, and July 12, 2018, 90 patients (45 with Ewing sarcoma 45 with osteosarcoma) were recruited to the study. Median follow-up was 31·3 months (95% CI 12·4–35·4) for patients with Ewing sarcoma and 31·1 months (24·4–31·7) for patients with osteosarcoma. 39 (87%) patients with Ewing sarcoma and 42 (93%) patients with osteosarcoma were assessable for efficacy after histological and radiological review. In patients with Ewing sarcoma, ten (26%; 95% CI 13–42) of 39 patients had an objective response (all partial responses) by 6 months; in patients with osteosarcoma, five (12%; 4–26) of 42 patients had an objective response (all partial responses) and 14 (33%; 20–50) had 6-month non-progression. The most common grade 3 or 4 adverse events were hypophosphataemia (five [11%] for Ewing sarcoma, three [7%] for osteosarcoma), aspartate aminotransferase increase (two [4%] for Ewing sarcoma, three [7%] for osteosarcoma), palmar-plantar syndrome (three [7%] for Ewing sarcoma, two [4%] for osteosarcoma), pneumothorax (one [2%] for Ewing sarcoma, four [9%] for osteosarcoma), and neutropenia (two [4%] for Ewing sarcoma, four [9%] for osteosarcoma). At least one serious adverse event was reported in 61 (68%) of 90 patients. No patients died from drug-related toxic effects. Interpretation Cabozantinib has antitumor activity in patients with advanced Ewing sarcoma and osteosarcoma and was generally well tolerated. Cabozantinib could represent a new therapeutic option in this setting, and deserves further investigation. Funding Institut Bergonié; French National Cancer Institute; Association pour la Recherche contre le Cancer.
dc.language.isoENen_US
dc.subjectEPICENE
dc.title.enCabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial
dc.title.alternativeLancet Oncolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/s1470-2045(19)30825-3en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
bordeaux.journalLancet Oncologyen_US
bordeaux.page446-455en_US
bordeaux.volume21en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue3en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamEPICENE_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03122528
hal.version1
hal.date.transferred2021-01-27T08:57:42Z
hal.exporttrue
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Lancet%20Oncology&amp;rft.date=2020&amp;rft.volume=21&amp;rft.issue=3&amp;rft.spage=446-455&amp;rft.epage=446-455&amp;rft.eissn=1474-5488%20(Electronic)%201470-2045%20(Linking)&amp;rft.issn=1474-5488%20(Electronic)%201470-2045%20(Linking)&amp;rft.au=ITALIANO,%20Antoine&amp;MIR,%20Olivier&amp;MATHOULIN-PELISSIER,%20Simone&amp;PENEL,%20Nicolas&amp;PIPERNO-NEUMANN,%20Sophie&amp;rft.genre=article


Fichier(s) constituant ce document

FichiersTailleFormatVue

Il n'y a pas de fichiers associés à ce document.

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée