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.