Co-targeting of cyclin and FGF/FGFR alterations with the CDK4/6 inhibitor palbociclib and the FGFR inhibitor lenvatinib can be carried out safely, with responses seen in three of six patients, including ongoing benefit in a patient with refractory osteosarcoma who continues to do well at 52+ months. The gene discussed is CDK4; the disease is osteosarcoma.