A Feasibility and Randomized Phase 2/3 Study of the VEFGR2/MET Inhibitor Cabozantinib in Combination with Cytotoxic Chemotherapy for Newly Diagnosed Osteosarcoma

Osteosarcoma is the most common primary bone malignancy of childhood and adolescence. Survival rates for patients with standard risk (localized, resectable primary tumors) and high-risk disease (presence of metastases, unresectable or primary pelvic tumors) are 70% and 20-30%, respectively, and have remained unchanged for several decades despite numerous attempts to augment standard therapies. Multi-targeted receptor tyrosine kinase inhibitors (MTKIs), such as cabozantinib, can target signaling pathways that are known to be altered in osteosarcoma. Several MTKIs including cabozantinib have recently shown clinical evidence of activity in prospective studies for both pediatric and adult patients with advanced osteosarcoma. Furthermore, feasibility of administering MTKIs in combination with cytotoxic chemotherapy has previously been shown in patients with AML, hepatocellular carcinoma, and soft tissue sarcomas. Osteosarcoma is the most common primary bone malignancy of childhood and adolescence. Survival rates for patients with standard risk (localized, resectable primary tumors) and high-risk disease (presence of metastases, unresectable or primary pelvic tumors) are 70% and 20-30%, respectively, and have remained unchanged for several decades