Real‐World Experience of Cabozantinib in Relapsed Osteosarcoma and Ewing Sarcoma—A Single Center Retrospective Study

ABSTRACT Aim Cabozantinib has demonstrated efficacy in advanced osteosarcoma and Ewing sarcoma. This study evaluated its real‐world outcomes in patients with relapsed osteosarcoma and Ewing sarcoma within Australia. Methods Retrospective investigation to evaluate real‐world outcomes of cabozantinib in patients with relapsed osteosarcoma or Ewing sarcoma at a high‐volume adult sarcoma center in Australia. Eligible patients were identified from a prospectively maintained institutional database. The primary endpoints were progression‐free survival (PFS) and overall survival (OS). Secondary endpoints were clinical benefit rate and treatment‐related adverse events (TRAEs). Results Between 2020 and 2025, 13 osteosarcoma and 2 Ewing sarcoma received cabozantinib. Median follow‐up was 12.9 (95% CI 8.6–NR) months. For the osteosarcoma cohort, median PFS was 4.3 (95% CI 2.6–6.9) months and median OS 9.8 (95% CI 6.0–NR) months. One Ewing sarcoma patient was deceased within 1 month of cabozantinib initiation, the other patient maintained tumor response at 5 months after initiation. First‐ versus later‐line use resulted in a median PFS of 5.4 versus 4.2 months, and median OS of 11.2 versus 7.7 months respectively. Clinical benefit rate was 38%. Nine (60%) patients required dose reduction due to TRAEs. Two patients developed pneumothoraces, leading to permanent discontinuation in one. Two patients discontinued due to decline in performance status, all others were due to disease progression. There was no treatment‐related mortality. Conclusion In this single‐center Australian analysis, cabozantinib showed activity in relapsed osteosarcoma and Ewing sarcoma with manageable TRAEs. Outcomes were comparable to those reported in the CABONE study and other real‐world series.