Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response.

There is a paucity of information about molecularly driven therapy in osteosarcomas. We report a 31-year-old woman with chemotherapy-refractory metastatic osteosarcoma who was successfully treated with the combination of palbociclib (CDK4/6 inhibitor) and lenvatinib (multikinase FGFR inhibitor), selected based on next generation sequencing that showed CDK4 and CCND2 amplifications (upregulates CDK4/6), and FGF6 (ligand for FGFR1,2 and 4), FGF23 (ligand for FGFR1,2,3, and 4) and FRS2 (adaptor protein for FGFR signaling) amplifications. The patient's tumor showed 68% reduction in positron emission tomography (PET) avidity, lasting 31 months after therapy initiation, when a solitary recurrence occurred, was resected, and treatment continued.