CDK4/6 inhibitors
Pills that stop the cell-division engine, added to hormone therapy for the most common type of breast cancer.
Palbociclib, ribociclib, abemaciclib with endocrine therapy: PFS roughly doubled and, for ribociclib and abemaciclib, overall survival improved in advanced HR+/HER2- disease. Ribociclib (NATALEE) and abemaciclib (monarchE) are approved as adjuvant therapy for high-risk early disease. 2026: palbociclib approved as maintenance in HR+/HER2+ disease (PATINA).
How it works
Block RB phosphorylation, arresting cells in G1.
- Oral, well tolerated
- Adjuvant survival benefit
- Neutropenia, diarrhoea (abemaciclib), QT (ribociclib)
- Resistance via RB loss, CDK2, cyclin E
Abemaciclib was the first CDK4/6 inhibitor approved after surgery for high-risk hormone-positive breast cancer.
A next-generation pill that blocks only CDK4, not CDK6, to keep the benefit of today's drugs without the low blood counts.
Palbociclib was the first CDK4/6 inhibitor (2015), and in 2026 became the first approved as maintenance in HER2-positive, hormone-positive breast cancer.
Ribociclib is the CDK4/6 inhibitor with the most consistent survival benefit, approved for a broad population of early breast cancer patients since 2024.
Ribociclib is a second adjuvant CDK4/6 option, and the only one with data in node-negative stage II disease. Roughly 3 in 100 patients avoid a relapse or death at three years, so the decision depends heavily on individual risk, tolerance of a three-year oral drug, and cost. Whether the benefit persists after treatment ends, as it did with abemaciclib, needs longer follow-up.
Women with hormone-receptor-positive, HER2-negative breast cancer that has spread to lymph nodes and has other high-risk features can now be offered two years of abemaciclib alongside their hormone therapy, with a durable reduction in relapse. It does not apply to node-negative or low-risk disease, and the diarrhoea and cost are real trade-offs to discuss.
Latest papers
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