(P 75) REAL-WORLD DATA ON REGORAFENIB AND CABOZANTINIB IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH RELAPSED OSTEOSARCOMA AND EWING SARCOMA INCLUDED IN THE SACHA-FRANCE STUDY

Objective: Regorafenib and cabozantinib have shown anti-tumor activity in patients with bone sarcomas at disease recurrence. Nevertheless, activity and safety data are mainly reported in adult patients with limited information on children/adolescents and young adults. We here report the nationwide real-world anti-tumor activity and toxicity of regorafenib and cabozantinib in patients with relapsed osteosarcoma and Ewing sarcoma included in the SACHA-France study (NCT04477681).

Methods: The SACHA-France study is a prospective, multicenter, national observational registry, open in all French Society of Pediatric Oncology (SFCE) centers, that collects clinical safety and efficacy data on innovative anticancer therapies first approved in adults after 2007 that are administered to patients ≤ 25 years-old with pediatric malignancies (solid tumor or leukemia) and prescribed either as compassionate or off-label use. All regorafenib and cabozantinib prescriptions for patients with relapsed osteosarcoma and Ewing sarcoma from 01/01/2020 to 31/12/2022 included in the SACHA-France registry are here analyzed.

Results: In the study period, 516 anticancer therapies prescribed to 485 patients were collected in SACHA-France. Regorafenib and cabozantinib represented 10% of all prescriptions (n=52), mostly in patients with osteosarcoma and Ewing sarcoma (n=46). Forty-four prescriptions were made at the time of disease recurrence in 18 SFCE centers (median 2 patients per center, range: 1-6 patients). Median age at regorafenib/cabozantinib prescription was 16,8 years (range: 6,9-24,4), compared to 11.2 years (range: 0.25-24.9) in the SACHA-France population. An objective response (partial/complete response) was reported in 4 patients out 44 patients (9%). 4-months PFS was 45%, with a median PFS of 97 days (range: 14-521). Patient’s characteristics and anti-tumor activity are presented in Table 1. Twelve patients (27%) continued with regorafenib/cabozantinib after tumor progression based on clinical benefit and/or lack of other therapies. In 23/44 patients (52%) at least a grade ≥2 clinical and/or grade ≥3 biological adverse drug reaction (ADR) was reported, leading to delayed therapy in 34% of patients. Overall, 5 serious ADRs were reported in 3 patients.

Conclusion: To our knowledge, this is the first comprehensive nation-wide study on regorafenib and cabozantinib prescriptions to children and adolescents and young adults with relapse osteosarcoma and Ewing sarcoma. In the real-life setting, safety profile is similar to that observed in other pediatric studies, with limited anti-tumor activity but prolonged clinical benefit in some patients.

Supported by Imagine for Margo, Association Hubert Gouin, Fondation du LEEM and the SFCE.