A systematic review of recent phase-II trials in refractory or recurrent osteosarcoma: Can we inform future trial design?
Clinical trial
Drug therapy
Osteosarcoma
Phase II
Recurrence
Systematic review
Journal
Cancer treatment reviews
ISSN: 1532-1967
Titre abrégé: Cancer Treat Rev
Pays: Netherlands
ID NLM: 7502030
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
22
07
2023
revised:
12
09
2023
accepted:
13
09
2023
pubmed:
23
9
2023
medline:
23
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis. 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. 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 H 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.
Sections du résumé
BACKGROUND/OBJECTIVE
OBJECTIVE
To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis.
METHODS
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
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 H
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 37738712
pii: S0305-7372(23)00118-4
doi: 10.1016/j.ctrv.2023.102625
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
102625Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [RE declares funding by the Princess Maxima foundation. KB declares honoraria for educational events for Novartis and has received honoraria for participation on advisory boards for glaxosmithkline, Bayer, NEC Oncoimmunity and Incyte. NE declares honoraria for educational events by Merck/MSD. NH declares a grant by the Swedish Childhood Cancer Fund. EP declares honoraria for participation on advisory boards for Deciphera Pharmaceutical, Eusa Pharma, SynOx Therapeutics and Daiichy Sankyo. SS declares consulting fees by Ceridwen Oncology, support for travel by Adaptimmune and has received honoraria for participation of an advisory board for glaxosmithkline. All remaining authors have declared no conflicts of interest.].