The evolving landscape of CDK4/6i therapy in metastatic BC: Experts discuss key findings and future directions

By Lisa Marie Basile | Fact-checked by MDLinx staff

Published March 9, 2025

Key Takeaways

Conference Buzz

“We’ve wondered about this for some time, based upon real world data, where we’d seen that patients get CDK4/6i after [a different] CDK4/6i… It is an emergent area, [and] things are rapidly changing, even in the last few months.” — Kevin Kalinsky, MD, MS, professor and director in the Division of Medical Oncology of the Department of Hematology and Medical Oncology at Emory Healthcare

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This article is part of our Miami Breast Cancer Conference 2025 coverage. Explore more.

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.^[]

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.

“It is an emergent area,” said Dr. Kalinsky. “Things are rapidly changing, even in the last few months.” He provided a little context, talking about the ever-changing landscape of HR+ metastatic BC—from tamoxifen in the 1970s, to the early 2000s’ fulvestran, through to today, with TROP2-targeted therapies like sacituzumab govitecan, datopotamab deruxtecan, and more.

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.

In HR+/HER2– patients with advanced BC who’d been administered prior ET and CDK4/6i therapies, the trial looked at abemcaciclib + fulvestrant vs placebo + fulvestrant. Importantly, the patients who were given abemaciclib had a significantly longer median PFS than the placebo arm.

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