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

article

N. Gaspar¹  Q. Campbell-Hewson²  S. Gallego Melcon³  F. Locatelli⁴  R. Venkatramani⁵  S. Hecker-Nolting⁶  M. Gambart⁷  F. Bautista⁸  E. Thebaud⁹  I. Aerts^1,10  B. Morland^1,11  C. Rossig^1,12  A. Canete Nieto^1,13  A. Longhi^1,14  C. Lervat^1,15  N. Entz-Werle^1,16  S.J. Strauss^1,17  P. Marec-Berard^1,18  C.E. Okpara^1,19  C. He^2,20  L. Dutta^2,21  M. Casanova^2,22 

[1] Department of Childhood and Adolescent Oncology, Gustave Roussy Cancer Campus;The Great North Children"s Hospital, Royal Victoria Infirmary;Pediatric Oncology and Hematology Service, University Hospital Vall d"Hebron;Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, University of Rome;Department of Pediatrics, Texas Children"s Cancer Center, Baylor College of Medicine;Department of Pediatric Oncology, Hematology, Immunology, Klinikum Stuttgart - Olgahospital;Pediatric Hemato-Oncology Unit, CHU Toulouse - Hôpital des Enfants;Paediatric Haematology-Oncology Department, Hospital Infantil Universitario Niño Jesús;Pediatric Oncology-Hematology and Immunology Department, CHU Nantes - Hôpital Mère-Enfant;SIREDO Oncology Center, Institut Curie, PSL Research University;Department of Paediatric Hematology/Oncology, Birmingham Children"s Hospital;Department of Pediatric Hematology and Oncology, University Children"s Hospital Muenster;Children"s Oncology Unit, Pediatric Service, Hospital Universitario y Politecnico La Fe;Chemotherapy Service, Istituto Ortopedico Rizzoli IRCCS;Pediatric and AYA Oncology Unit, Centre Oscar Lambret Lille;Pediatric Onco-Hematology Unit, Chu Strasbourg-Hôpital Hautepierre;Clinical Research Facility, University College London Hospitals NHS Trust;Institute of Pediatric Hematology and Oncology, Centre Léon Bérard;Clinical Research, Oncology Business Group, Eisai Ltd.;Biostatistics, Oncology Business Group, Eisai Inc.;Clinical Research, Oncology Business Group, Eisai Inc.;Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori

关键词: lenvatinib;    osteosarcoma;    pediatric;    solid tumors;    tyrosine kinase inhibitors;   

DOI  :  10.1016/j.esmoop.2021.100250

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background 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).

【 授权许可】

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