Treatment of Cancers with MDM2 and CDK4 Overexpression

Introduction to CDK4/6 Inhibitors

The American Society of Clinical Oncology recommends CDK4/6 inhibitors combined with endocrine therapy as the standard-of-care for ER-positive, HER2-negative metastatic breast cancer, demonstrating improved progression-free survival and overall survival with a manageable toxicity profile 1, 2
The European Society for Medical Oncology suggests that three approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) show similar efficacy in the metastatic setting, though their toxicity profiles differ slightly 3, 4

For patients who did not relapse on aromatase inhibitors or within 12 months of stopping adjuvant aromatase inhibitors, the National Comprehensive Cancer Network recommends a CDK4/6 inhibitor plus aromatase inhibitor 2, 3
For patients who relapsed on adjuvant aromatase inhibitor therapy or within 12 months of stopping adjuvant aromatase inhibitors, the American College of Physicians recommends a CDK4/6 inhibitor plus fulvestrant 2, 3

The American Society of Clinical Oncology notes that after progression on CDK4/6 inhibitors, options include fulvestrant-alpelisib for PIK3CA-mutated tumors, exemestane-everolimus, or other endocrine-based therapies 3, 4
The European Society for Medical Oncology states that while adjuvant CDK4/6 inhibitors have shown improved invasive disease-free survival in high-risk early breast cancer, there are concerns about lack of overall survival benefit and potential induction of resistance 5, 6
The National Comprehensive Cancer Network reports that the financial burden of these therapies is substantial, especially for CDK4/6 inhibitors, which cost approximately $5,000 per patient monthly 5