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Cited by 19Sarcoma Diagnosis and TreatmentBone Tumor Diagnosis and TreatmentsStatistical Methods in Clinical Trials

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

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van Ewijk, Roelof, Cleirec, Morgane, Herold, Nikolas, le Deley, Marie-Cécile, van Eijkelenburg, Natasha, Boudou-Rouquette, Pascaline, Risbourg, Séverine, Strauss, Sandra J. +6 more·2023·Cancer Treatment Reviews
DOI 10.1016/j.ctrv.2023.102625
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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 H 1 /H 0 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.

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  • Systemic treatment for advanced bone sarcoma progressing after upfront chemotherapy is challenging, with best results still leveraging ifosfamide for Ewing sarcoma and osteosarcoma, whereas evidence is limited in dedifferentiated chondrosarcoma, conventional chondrosarcoma, and other ultra-rare bone sarcomas.

    “Systemic treatment for advanced bone sarcoma (BS) progressing after upfront chemotherapy is challenging, with best results still leveraging on the use of ifosfamide both for Ewing sarcoma 1 and osteosarcoma, 2 , 3 whereas evidence is limited in dedifferentiated chondrosarcoma (DDCS), 4 conventional chondrosarcoma 5 and other ultra‐rare BS. 6”

    From Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial (2025) · cites this paper as [3]

  • In a recent review of 27 trials of systemic treatments for relapsed osteosarcoma, including chemotherapy and TKI, the median PFS was 3 months (range, 1.2-19.4).

    “in a recent review of 27 trials of systemic treatments for patients with osteosarcoma relapsed, including chemotherapy and TKI, the median PFS was 3 months (range, 1.2–19.4). 3”

    From Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial (2025) · cites this paper as [3]

  • For patients with unresectable or refractory osteosarcoma following first-line chemotherapy, prognosis remains poor, with 5-year post-relapse survival rates below 20%.

    “For patients with unresectable or refractory osteosarcoma following first-line chemotherapy, prognosis remains poor, with 5-year post-relapse survival rates below 20%16,17.”

    From Apatinib plus ifosfamide and etoposide versus ifosfamide and etoposide in patients with advanced osteosarcomas (OAIE/PKUPH-sarcoma 11): a randomized phase II study (2025) · cites this paper as [17]

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Authors
van Ewijk, R., Cleirec, M., Herold, N., le Deley, M.-C., van Eijkelenburg, N., Boudou-Rouquette, P., Risbourg, S., Strauss, S. J., Palmerini, E., Boye, K., Kager, L., Hecker-Nolting, S., Marchais, A., & Gaspar, N.
Affiliations
  • Centre Hospitalier Universitaire de Nantes (FR)
  • Karolinska University Hospital (SE)
  • Centre Oscar Lambret (FR)
  • University College London (GB)
  • Istituto Ortopedico Rizzoli (IT)
  • Oslo University Hospital (NO)
  • St Anna Children's Hospital (AT)
  • Inserm (FR)
Corresponding author
Gaspar, Nathalie
ORCID
Venue
Cancer Treatment Reviews
Publisher
Elsevier BV
Published
2023-11
Volume
120
Pages
102625
ISSN
0305-7372 (ISSN-L)
DOI
10.1016/j.ctrv.2023.102625
OpenAlex
W4386786228
Cited by
19
References
98
Citations by year
2026: 5 · 2025: 8 · 2024: 6
FWCI
0.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Treatment Reviews (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc-nd)
  • UCL Discovery (University College London) (submittedVersion, cc-by-nc-nd)
Funders
  • Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent
  • Myrovlytis Trust
  • Institut Gustave-Roussy
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Keywords
recurrent osteosarcoma, trial design, multikinase inhibitor, primary endpoint, patient selection, clinical trial registries
MeSH terms
Bone Neoplasms, Humans, Neoplasm Recurrence, Local, Research Design, Osteosarcoma, Clinical Trials, Phase II as Topic

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