(P 121) REAL-WORLD EXPERIENCE OF CABOZANTINIB MONOTHERAPY IN RELAPSED OR REFRACTORY OSTEOSARCOMA AND EWING SARCOMA: A SINGLE-CENTRE AUSTRALIAN STUDY

Objective: Cabozantinib (CBZ) has demonstrated efficacy in advanced osteosarcoma and Ewing sarcoma (ES) per the CABONE study (Italiano et al, Lancet Oncol. 2020). This study aimed to evaluate the real-world efficacy and safety of CBZ in relapsed or refractory osteosarcoma and ES in the Australian context.

Methods: We conducted a retrospective single-centre study to assess the real-world outcomes of CBZ monotherapy in relapsed or refractory osteosarcoma or ES.

Results: Between November 2022 and June 2025, 14 patients (pts) received CBZ monotherapy, 13 osteosarcoma and 1 ES. Median age was 30 (range 18-56) years and 8 were male (57%). 8 (57%) pts had received ≥ 2 lines of prior systemic therapy. All pts commenced CBZ at 60mg. At analysis cutoff with a median follow-up of 8.4 months, 4 (29%) pts remained on CBZ, 10 (71%) pts had ceased due to disease progression. Median duration of treatment was 7 months (range 0.5-NR). Best overall response was 3 (21%) partial response, 5 (36%) stable disease (4 for ≥ 6 months), 6 (43%) progressive disease. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2-7.2). 6-month PFS rate was 43%. One patient achieved a near complete metabolic response following 6 weeks of CBZ. Another patient maintained a durable partial response for 18 months. Median overall survival was 9.0 months (95% CI 4.1-NA). In the relapsed/refractory setting, first-line use of CBZ resulted in a median PFS of 7.1 months (n=6); second- and later-line use resulted in a median PFS of 2.6 months (n=8). Following progression (n=9), one patient received oral etoposide, one received palliative radiation therapy, the remainder (n=7) did not receive further anti-cancer therapy. Most common adverse events were nausea (50%, G1/2), mucositis (43%, G1), diarrhoea (36%, G1/2), hepatotoxicity (36%, G2) and fatigue (29%, G1). 5 (36%) pts required dose reduction to 40mg due to G2 hepatotoxicity and 4 (29%) pts due to multiple concurrent G1/2 toxicities (fatigue, mucositis, diarrhoea). There were no withdrawals or deaths due to toxicity.

Conclusion: Our real-world data showed that CBZ monotherapy has clinically meaningful activity in osteosarcoma and ES, with acceptable toxicities. Validation in larger cohorts is warranted.