Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are medications used to inhibit enzymes involved in cell division. (Drugs include palbociclib, ribociclib, and abemaciclib.) CDK4/6 inhibitors have become a standard-of-care in certain breast cancer (BC) patients, and can also be used as adjuvant therapy in higher-risk BC patients who have been diagnosed early.

Morrison L, Loibl S, Turner NC. The CDK4/6 inhibitor revolution — a game-changing era for breast cancer treatment. Nat Rev Clin Oncol 21, 89–105 (2024). doi.org/10.1038/s41571-023-00840-4.

Here are the latest insights on this class of drugs, coming from the experts speaking at Miami Breast Cancer Conference 2025.

In HR+ metastatic BC

Kevin Kalinsky, MD, MS, professor and director in the Division of Medical Oncology of the Department of Hematology and Medical Oncology at Emory Healthcare, discussed retreatment with CDK4/6i in HR+ metastatic BC.

The session focused on endocrine-sensitive BC, with Dr. Kalinsky highlighting a few trials, including the MAINTAIN trial, which found a “significant progression-free survival benefit” for patients with HR+/HER2 metastatic breast cancer who switched endocrine therapy (ET) and received ribociclib compared with placebo after prior CDK4/6i treatment and different ET.

Trials to know

He also highlighted the PACE trial, which found that “the addition of palbociclib to fulvestrant did not improve PFS vs fulvestrant alone among patients with HR+/HER2– MBC whose disease had progressed on a previous CDK4/6i plus [aromatase inhibitor]. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.”

And then there was the MONARCH trial—the only phase 3 trial that looked at CDK4/6i use after treating with a different CDK4/6i.

The takeaway? For certain patients, in certain cases, “We do have the option of giving a CDK4/6i after CDK4/6i,” Dr. Kalinsky said.