EVERolimus and LenvAtinib Versus Everolimus for Bone Sarcoma

Those studies demonstrate strong rationale to combine a multikinase inhibitor targeting VEGFR, PDGFR with mTOR inhibitor. Moreover, another multi-targeted TKI, lenvatinib monotherapy showed promising activity in osteosarcoma. Therefore, clinical trial with Lenvatinib in combined with everolimus is ongoing for solid tumors (NCT03245151). Considering lenvatinib and everolimus (18 mg/day and 5 mg/day) already approved as standard treatment for renal cell carcinoma based on the powerful ORR, PFS, and OS14, these noteworthy findings advance the treatment paradigm for bone sarcoma patients. Because all those trials for sarcoma were done in the absence of a control group, based on such clinical studies, a confirmatory trial comparing mTOR inhibitor and a multi-targeted tyrosine kinase inhibitor (multi-TKI) combination versus monotherapy is essential. Therefore, we planned to conduct the randomized phase II trial of everolimus in combination with lenvatinib for advanced/metastatic bone sarcomas. In addition, we will explore predictive biomarkers by repeated biopsies and blood samplings during the treatment.