Case report of combination strategy for osteosarcoma with cell cycle and fibroblast growth factor genomic alterations

There is a paucity of information about molecularly driven therapy in osteosarcomas. A patient of University of California San Diego had chemotherapy-refractory metastatic osteocarcoma. Next generation sequencing of tumor tissue revealed CDK4 and CCND2 amplifications (upregulates CDK4/6) and fibroblast growth factor genomic alterations. USCD molecular tumor board advised combination therapy with the CDK4/6 inhibitor palbociclib plus the multikinase FGFR inhibitor lenvatinib. The patient remained on therapy for 51+ months, with excellent tolerance and continued response. The authors conclude that co-targeting the aberrant cyclin and FGFR pathways resulted in long-term exceptional response in a patient with refractory advanced osteosarcoma.