(P 57) REAL-WORLD EXPERIENCE OF CABOZANTINIB IN PAEDIATRIC, TEENAGE AND YOUNG ADULT (TYA) AND ADULT METASTATIC BONE SARCOMA PATIENTS FROM THE LONDON SARCOMA SERVICE (LSS)

Objective: Sarcomas are rare, highly heterogenous solid tumours. Osteosarcoma (OS) and Ewing Sarcoma (ES) are the most common bone malignancies in children and young adults. Patients with relapsed OS and ES have a median overall survival of 12 – 18 months. Treatment options for advanced sarcoma are limited. Cabozantinib is an oral multi-kinase inhibitor (MET, VEGFR, AXL) that has demonstrated relevant pre-clinical efficacy in OS and ES. Moreover, the phase II CABONE trial demonstrated anti-tumour activity of cabozantinib in OS and ES patients with an overall response rate (ORR) of 11.9% and 19% respectively. Median progression free survival (PFS) was 6.7 months.

This study reports the real-world experience of bone sarcoma patients treated with cabozantinib within the London Sarcoma Service (LSS).

Methods: Single centre retrospective analysis of paediatric, teenage and young adult (TYA) and adult metastatic bone sarcoma patients treated with compassionate-use cabozantinib within the LSS between May 2021 and May 2023.
Patients were identified using a local electronic health record system. Patients were radiologically evaluated according to standard of care, most commonly after two or three cycles of treatment (8-12 weeks). Clinical benefit was defined as lack of clinical or radiological progression. Drug related adverse events were assessed using CTCAE version 5. Time on treatment and cabozantinib dose, including dose modification, were also assessed.

Results: Twenty-four patients were identified with a median age of 23 years (range 13-63); three paediatric patients ( < 16 years), eight TYA patients (16 – 24 years) and thirteen adult patients (>25 years). Diagnoses included OS (n=16), ES (n=6) and other diagnoses (n=2) which included BCOR-CCNB3 sarcoma and mesenchymal chondrosarcoma. Median number of prior therapies was 3 (range 1 - 7). Median time from diagnosis to commencing cabozantinib was 34 weeks (range 6 - 203).

The median duration on treatment was 12.5 weeks across all ages (range 2 – 105); 8 weeks for paediatric/TYA patients and 14 weeks for adults. Eight patients remain on treatment. The most common reported drug-related grade 3 adverse events were pneumothorax (n=2), proteinuria (n=1), fatigue (n=2), rash (n=1), hypothyroidism (n=1), myalgia (n=1) and mucositis (n=1) (Figure 1).

Sixteen patients commenced treatment on 60mg daily. Five of these patients (31%) required a dose reduction to 40mg. Eight patients commenced on 40mg daily and dose escalation to 60mg was possible for three of these patients.

Eighteen patients (75%) were available for best radiological assessment at a median of 11 weeks (range 5 to 21) after starting treatment. Eight patients showed clinical benefit; one patient demonstrated a partial response, six had stable disease and one had a mixed response. Ten patients showed progressive disease. In paediatric/TYA patients the primary reason for treatment discontinuation was progressive disease (six of eleven patients). In the adult population four of five patients stopped treatment due to toxicity and lack of clinical benefit. Median overall survival on cabozantinib was 5.3 months (range 1.6 – 26.4), with nine patients still alive (Figure 2).

Conclusion: In patients with recurrent, metastatic bone sarcomas, cabozantinib may offer benefit for select patients, but overall outcomes were poor with treatment-related toxicity that requires monitoring. Its use in combination with adjuvant chemotherapy or maintenance therapy may lead to better outcomes and should be explored within randomised clinical trials. International collaborative prospective ‘real world’ data registries, such as the SACHA study may provide additional insights.