The clinical trial landscape of osteosarcoma: integrating trial data, immunotherapeutic trends, and biomarker insights

Cancer research · Osteosarcoma

We systematically analysed 864 interventional osteosarcoma trials from TrialTrove (as of September 2025).

Osteosarcoma, the most aggressive primary malignant bone tumour, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5‑year overall survival (OS) is <30 % for metastatic/recurrent cases. Genomic heterogeneity, an immunosuppressive tumour micro‑environment (TME) and low immunogenicity limit the efficacy of emerging immunotherapies, which lack large‑scale clinical validation. We systematically analysed 864 interventional osteosarcoma trials from TrialTrove (as of September 2025). Trial numbers peaked at 54 in 2021, with 77.3 % past (completed/terminated) and over 94 % in phase I/II (only 3.6 % phase III‑IV). The U.S. dominated (60.9 %), focusing on immunotherapy/targeted therapy; low‑ and middle‑income countries (LMICs) accounted for < 2 % of trials despite bearing 40 % of the global disease burden. Conventional chemotherapy remains the cornerstone; immuno‑oncology (540 trials) is the leading novel strategy, with top targets VEGFR2 (104), PD‑1 (70) and mTOR (60). Biomarker use was imbalanced: liver/nutritional markers prevailed, whereas key immune/genomic biomarkers (CD8A, TP53) were under‑represented (< 8 % combined). Key challenges include severe trial‑phase imbalance, global disparities and preclinical‑clinical gaps; opportunities lie in synergistic novel therapies (ICI combinations, GD2‑targeted CAR‑T) and decentralized clinical trials (DCT). Future priorities: accelerate late‑phase trials for promising regimens, reduce global disparities via regional consortia, integrate precision biomarkers for patient stratification, and translate TME insights into trials. This analysis highlights the need to shift from conventional chemotherapy optimisation to precision‑driven, globally equitable strategies to improve outcomes for high‑risk osteosarcoma patients.

The analysis reveals that the evidence base for osteosarcoma therapies is dominated by early‑phase, single‑agent studies, with a striking lack of late‑phase confirmatory trials. By characterising the distribution of therapeutic targets, biomarker usage and trial numbers across countries, the paper identifies the gaps that must be addressed to accelerate the development of effective, precision‑driven treatments for patients with metastatic or recurrent osteosarcoma.

Evidence level: Állatkísérletes. Állatmodellben vizsgálták.

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