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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorGaspar, N.
dc.contributor.authorCampbell-Hewson, Q.
dc.contributor.authorGallego Melcón, Soledad
dc.contributor.authorLocatelli, F.
dc.contributor.authorVenkatramani, R.
dc.contributor.authorHecker-Nolting, S.
dc.date.accessioned2022-04-25T13:16:10Z
dc.date.available2022-04-25T13:16:10Z
dc.date.issued2021-10
dc.identifier.citationGaspar N, Campbell-Hewson Q, Gallego Melcon S, Locatelli F, Venkatramani R, Hecker-Nolting S, et al. Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050). ESMO Open. 2021 Oct 1;6(5):100250.
dc.identifier.issn2059-7029
dc.identifier.urihttp://hdl.handle.net/11351/7399
dc.descriptionOsteosarcoma; Pediatric; Solid tumors
dc.description.abstractBackground We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). Patients and methods The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. Results In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan–Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. Conclusions The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755).
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesESMO Open;6(5)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectOssos - Malalties, en els infants
dc.subjectOssos - Càncer - Tractament
dc.subjectQuimioteràpia combinada
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshBone Neoplasms
dc.subject.mesh/drug therapy
dc.titlePhase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.esmoop.2021.100250
dc.subject.decsprotocolos de quimioterapia antineoplásica combinada
dc.subject.decsneoplasias óseas
dc.subject.decs/farmacoterapia
dc.relation.publishversionhttps://doi.org/10.1016/j.esmoop.2021.100250
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Gaspar N] Department of Childhood and Adolescent Oncology, Gustave Roussy Cancer Campus, Villejuif, France. [Campbell-Hewson Q] The Great North Children's Hospital, Royal Victoria Infirmary, Newcastle Upon Tyne, UK. [Gallego Melcon S] Servei d'Oncologia i Hematologia Pediàtrica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Locatelli F] Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, University of Rome, Rome, Italy. [Venkatramani R] Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, USA. [Hecker-Nolting S] Department of Pediatric Oncology, Hematology, Immunology, Klinikum Stuttgart - Olgahospital, Stuttgart, Germany
dc.identifier.pmid34562750
dc.identifier.wos000704803800003
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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