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A systematic review of recent phase-II trials in refractory or recurrent osteosarcoma: Can we inform future trial design?

van Ewijk, Roelof; Cleirec, Morgane; Herold, Nikolas; le Deley, Marie-Cécile; van Eijkelenburg, Natasha; Boudou-Rouquette, Pascaline; Risbourg, Séverine; ... FOSTER Consortium, .; + view all (2023) A systematic review of recent phase-II trials in refractory or recurrent osteosarcoma: Can we inform future trial design? Cancer Treatment Reviews , 120 , Article 102625. 10.1016/j.ctrv.2023.102625. (In press). Green open access

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Abstract

Background/Objective: To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis.// Methods: A systematic review of trials registered on trial registries between 01/01/2017–14/02/2022. Comparison of 98 trials identified between 2003 and 2016. Publication search/analysis for both periods, last update on 01/12/2022.// Results: Between 2017 and 2022, 71 phase-II trials met our selection criteria (19 osteosarcoma-specific trials, 14 solid tumor trials with and 38 trials without an osteosarcoma-specific stratum). The trial number increased over time: 13.9 versus 7 trials/year (p = 0.06). Monotherapy remained the predominant treatment (62% vs. 62%, p = 1). Targeted therapies were increasingly evaluated (66% vs. 41%, P = 0.001). Heterogeneity persisted in the trial characteristics. The inclusion criteria were measurable disease (75%), evaluable disease (14%), and surgical remission (11%). 82% of the trials included pediatric or adolescent patients. Biomarker-driven trials accounted for 25% of the total trials. The survival endpoint use (rather than response) slightly increased (40% versus 31%), but the study H1/H0 hypotheses remained heterogeneous. Single-arm designs predominated over multiarm trials (n = 7). Available efficacy data on 1361 osteosarcoma patients in 58 trials remained disappointing, even though 21% of these trials were considered positive, predominantly those evaluating multi-targeted kinase inhibitors.// Conclusion: Despite observed changes in trial design and an increased number of trials investigating new therapies, high heterogeneity remained with respect to patient selection, study design, primary endpoints, and statistical hypotheses in recently registered phase II trials for osteosarcoma. Continued optimization of trial design informed by a deeper biological understanding should strengthen the development of new therapies.

Type: Article
Title: A systematic review of recent phase-II trials in refractory or recurrent osteosarcoma: Can we inform future trial design?
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ctrv.2023.102625
Publisher version: https://doi.org/10.1016/j.ctrv.2023.102625
Language: English
Additional information: © The Author(s), 2023. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CC-BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Osteosarcoma, Drug therapy, Recurrence, Clinical trial, Phase II, Systematic review
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10178055
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