Real‐world experience of tyrosine kinase inhibitors in children, adolescents and adults with relapsed or refractory bone tumours: A Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) study
Open accessAbstract
Objectives: We conducted a retrospective multi‐centre study to assess the real‐world outcome of regorafenib (REGO) and cabozantinib (CABO) in recurrent/refractory bone tumours (BTs) including osteosarcoma (OST), Ewing sarcoma (EWS) and chondrosarcoma (CS)/extra‐skeletal mesenchymal CS (ESMC). Methods: After regulatory approval, data from patients with recurrent BT (11 institutions) were extracted from CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) database. Patient characteristics, treatment and outcomes were collected. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: From July 2018 to May 2022, 66 patients received REGO or CABO; 39 OST, 18 EWS, 4 CS and 5 ESMC. Median age was 27.8 years (range 12–76); median starting dose was 60 mg for CABO (n = 37, range 40–60) and 120 mg for REGO (n = 29, range 40–160). Twenty‐eight (42.4%) patients required dose reduction: hand‐foot syndrome 7 (10.6%), nausea/vomiting 1 (1.5%), diarrhoea 1 (1.5%), 2 elevated LFTs (3%), elevated bilirubin 1 (1.5%) and mucositis 1 (1.5%). The median OS for patients with OST, EWS, CS and ESMC was 8.5 months (n = 39, 95% CI 7–13.1); 13.4 months (n = 18, 95% CI 3.4–27.2), 8.1 (n = 4, 95% CI 4.1–9.3) and 18.2 (n = 5, 95% CI (10.4–na), respectively. Median PFS for OST, EWS, CS and ECMS was 3.5 (n = 39, 95% CI 2.8–5), 3.9 (n = 18, 95% CI 2.1–5.9), 5.53 (n = 4. 95% CI 2.13–NA) and 11.4 (n = 5, 95% CI 1.83–14.7), respectively. Age, line of therapy, REGO versus CABO, or time from diagnosis to initiation of TKI were not associated with PFS on univariable analysis. Conclusion: Our real‐world data show that TKIs have meaningful activity in recurrent BT with acceptable toxicities when started at modified dosing. Inclusion of TKIs in earlier lines of treatment and/or maintenance therapy could be questions for future research.
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Approximately 40% of patients remained progression-free for more than 5 months.
“approximately 40% of the patients remained progression–free for more than 5 months”
From Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial (2025) · cites this paper as [40]
The Results > Outcome section (page unavailable) describes patients who remained without progression for more than five months, including two for over 16 months. It does not report that approximately 40% of patients met that threshold; its percentages describe other measures or time periods. (LLM, conf=0.77)
Experimental — accuracy not yet measuredThe observed tumor stabilization qualifies as active treatment in the setting of high-grade sarcomas.
“the observed tumor stabilization was important, and approximately 40% of the patients remained progression–free for more than 5 months, which qualifies as active treatment in the setting of high‐grade sarcomas. 39 , 40 , 41 , 42”
From Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial (2025) · cites this paper as [40]
The Methods define stable disease lasting more than three months as clinical benefit, and the Discussion describes prolonged disease stability and meaningful activity from tyrosine kinase inhibitors. This supports treating stabilization as a meaningful outcome in the relapsed or refractory bone tumours studied, but the paper does not establish it as a criterion for active treatment across high-grade sarcomas generally. (LLM, conf=0.82)
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- Authors
- Peretz Soroka, H., Vora, T., Noujaim, J., Marcoux, N., Cohen‐Gogo, S., Alcindor, T., Holloway, C., Rodrigues, C., Karachiwala, H., Alvi, S., Lee, U., Cheng, S., Banerji, S., Oberoi, S., Feng, X., Smrke, A., Simmons, C., Razak, A. A., & Gupta, A. A.
- Affiliations
- Division of Medical Oncology, Princess Margaret Cancer Centre University of Toronto Toronto Ontario Canada
- University of Toronto (CA)
- Hôpital Maisonneuve-Rosemont (CA)
- Centre hospitalier universitaire de Québec (CA)
- McGill University Health Centre (CA)
- University of British Columbia (CA)
- Alberta Health Services (CA)
- Division of Pediatric Hematology/Oncology Jim Pattison Children's Hospital Saskatoon Saskatoon Saskatchewan Canada
- BC Cancer Agency (CA)
- CancerCare Manitoba (CA)
- Mount Sinai Hospital (CA)
- Corresponding author
- Gupta, Abha A.
- ORCID
- Venue
- Cancer Medicine
- Publisher
- Wiley
- Published
- 2023-09
- Volume
- 12
- Issue
- 18
- Pages
- 18872-18881
- ISSN
- 2045-7634 (ISSN-L)
- PMC
- PMC10557866
- OpenAlex
- W4386845937
- Cited by
- 17
- References
- 27
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 3 · 2023: 2
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- tyrosine kinase inhibitors, regorafenib, cabozantinib, osteosarcoma, Ewing sarcoma, chondrosarcoma, extraskeletal mesenchymal chondrosarcoma, progression-free survival, overall survival, hand-foot syndrome, dose reduction, real-world outcomes, sarcoma treatment, children and adolescents
- MeSH terms
- Tyrosine Kinase Inhibitors, Adolescent, Adult, Aged, Bone Neoplasms, Canada, Child, Chondrosarcoma, Humans, Middle Aged, Neoplasm Recurrence, Local, Phenylurea Compounds, Pyridines, Retrospective Studies, Sarcoma, Sarcoma, Ewing, Osteosarcoma, Soft Tissue Neoplasms, Young Adult
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