Unexpected toxicity of CDK4/6 inhibitor palbociclib and radiotherapy

Background Cyclin-dependent kinase (CDK) 4/6 inhibitors have recently been approved for the treatment of hormone receptor-positive and HER2-negative metastatic breast cancer in association with endocrine therapy in postmenopausal women. Data on the interaction of CDK4/6 inhibition and radiotherapy are scarce, but some studies show unexpected toxicity. Cases We report three cases of unexpected severe or prolonged soft tissue, skin, and gastrointestinal toxicity in patients treated with a combination of radiotherapy and the CDK4/6 inhibitor palbociclib. Conclusion These cases indicate a possible interaction between radiotherapy and palbociclib. Therefore, we recommend using radiotherapy cautiously when combined with CDK4/6 inhibitors.