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Blood & Cancer episode 10:
CDK4/6 inhibitors in breast cancer
Richard Finn, MD, of the Geffen School of Medicine at UCLA joins guest host Jame Abraham, MD, of the Cleveland Clinic to discuss CDK4/6 inhibitors in the treatment of breast cancer, from the first pivotal studies to efficacy and patient selection.
Later, Ilana Yurkiewicz, MD, talks about why it’s problematic to tell patients there is no more treatment in this week’s Clinical Correlation. Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford University and is also a columnist for Hematology News.
By Emily Bryer, DO, Resident in the department of internal medicine, University of Pennsylvania.
- Cyclin dependent kinase 4 and 6 (CDK4/6) control phosphorylation of the retinoblastoma gene product in the G1 to S transition of the cell cycle.
- Luminal ER-positive HER2-negative breast cancers are most sensitive to inhibition with a CDK4/6 inhibitor and act synergistically with tamoxifen.
- PALOMA 1 trial studied CDK4/6 Inhibitors in ER-positive breast cancer.
- Letrozole alone (10-month PFS) versus letrozole plus palbociclib (greater than 20-month PFS)
- Toxicity = grade 3 (ANC 500-1000) and grade 4 neutropenia (ANC less than 500)
- Low incidence of neutropenic fever
- Palbociclib and chemotherapy have distinct effects on the bone marrow.
- Palbociclib is cytostatic (also, toxicity is predictable and not cumulative)
- Chemotherapy is cytocidal
- Although efficacy is similar between CDK4/6 inhibitors (PFS hazard ratio +/-0.5), side effects vary.
- Ribociclib and palbociclib have a higher incidence of neutropenia
- Ribociclib affects QTC interval and liver enzymes
- Abemaciclib is associated with diarrhea and venous thromboembolism
- Ongoing studies are exploring 1) CDK4/6 inhibitor plus endocrine therapy versus endocrine therapy alone and 2) CDK4/6 inhibitors in the adjuvant setting.
- The population to most benefit from CDK4/6 inhibitors may include the patients who are high-risk for relapse following endocrine therapy alone (previously those who would also receive chemotherapy).
- N Engl J Med 2018; 379:1926-36.
- Breast Cancer. 2018 Jul;25(4):402-6.