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

Cancer Med. 2023 Sep;12(18):18872-18881. doi: 10.1002/cam4.6515. Epub 2023 Sep 19.

Abstract

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.

Keywords: CanSaRCC; Ewing sarcoma; cabozantanib; chondrosarcoma; osteosarcoma; regorafenib.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / pathology
  • Canada
  • Child
  • Chondrosarcoma*
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Osteosarcoma* / pathology
  • Retrospective Studies
  • Sarcoma* / drug therapy
  • Sarcoma, Ewing* / drug therapy
  • Sarcoma, Ewing* / pathology
  • Soft Tissue Neoplasms*
  • Tyrosine Kinase Inhibitors
  • Young Adult

Substances

  • Tyrosine Kinase Inhibitors
  • regorafenib