SABCS 2025: Expert Perspective on CDK4/6 Inhibitor Use in Metastatic Hormone Receptor-Positive Breast Cancer
Key Points
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Ribociclib has become the preferred CDK4/6 inhibitor in metastatic hormone receptor (HR)-positive breast cancer, largely driven by the MONALEESA trials’ overall survival (OS) data and its tolerability.
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Prior adjuvant CDK4/6 inhibitor use may complicate sequencing decisions in the metastatic setting, with trial design differences and patient risk profiles guiding individualized choices.
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Treatment selection, especially when considering long-term therapy, should be guided by patient quality of life (QoL), symptom burden, and financial toxicity.
As more patients with HR-positive breast cancer receive CDK4/6 inhibitors earlier in their disease course, clinicians are focused on how to sequence these agents upon recurrence. Based on OS data from the MONALEESA trials, ribociclib has emerged as a favored option in the metastatic setting. Furthermore, its safety profile also makes it a good choice, according to Matthew Kurian, MD, of St. Elizabeth Healthcare.
At the 2025 San Antonio Breast Cancer Symposium (SABCS 2025), Dr. Kurian discussed CDK4/6 inhibitor use with Elia Segui Solis, MD, of Dana-Farber Cancer Institute. Although ribociclib carries the risk of liver enzyme elevations, QTc prolongation, and gastrointestinal toxicity, these side effects are well understood, monitored, and generally manageable, said Dr. Kurian. Therefore, many clinicians who previously used multiple CDK4/6 inhibitors now default to ribociclib as a first-line treatment in metastatic disease. In cases of toxicity, palbociclib is often well-tolerated.
Decision-making becomes more challenging when recurrence occurs after adjuvant CDK4/6 inhibitor therapy. Dr. Kurian explained that the differences between the monarchE and NATALEE trials, including patient populations and study endpoints, limit direct comparisons. While monarchE demonstrated an OS benefit with abemaciclib, NATALEE evaluated invasive disease-free survival as the primary endpoint. Risk stratification remains key, with nodal status, genomic risk, tumor grade, and size informing whether ribociclib or abemaciclib is selected, particularly in patients who may meet criteria for both agents, he said.
The data presented at SABCS 2025 also highlighted the growing importance of QoL considerations, patient-reported outcomes, and financial toxicity. With novel endocrine strategies and the potential of long-term therapy extending 5 to 10 years or more, clinicians emphasized the need to balance disease control with day-to-day well-being.