Navigating Treatment Decision-Making for CDK4/6 Inhibitors in Breast Cancer

Hope S. Rugo, MD, spoke with CancerNetwork^® at the 2025 International Congress on the Future of Breast Cancer East hosted by Physicians Education Resource LLC^® about various considerations for treatment decision-making with CDK4/6 inhibitors among different patient populations with breast cancer.

According to Rugo, patients with high-risk disease may be offered therapy with CDK4/6 inhibitors based on a conversation regarding toxicity profiles, duration of therapy, and length of currently available efficacy data. On the other hand, those with node-negative disease are offered this class of agents more judiciously based on criteria established in the phase 3 NATALEE trial (NCT03701334) assessing ribociclib (Kisqali) plus endocrine therapy in early breast cancer.

Rugo is a professor in the Department of Medical Oncology & Therapeutics Research, division chief of Breast Medical Oncology, and director of the Women’s Cancers Program at City of Hope in Duarte, California.

Transcript:

What do we do in the clinic? It’s clear that patients with high-risk disease—1 to 3 positive nodes with other high-risk features—those are patients where we’re frustrated with a lack of ability to give the best therapy. We give everything that’s part of the guidelines and treatment, and we see unacceptable rates of recurrence. [When] these patients are offered CDK4/6 inhibitors....you have to decide with the patient on what the right treatment is for them, [considering] the [adverse] effect profile, the duration of therapy, and the length of efficacy data that are available. The big question that comes up for us is, “Which patients with node-negative disease should be treated?” We’re using the NATALEE criteria now, but judiciously. A patient who’s a lot older, has other comorbidities that may impact the treatment, or has a huge share of cost in our current environment in the US—[the regimen] may not be the right balance at the moment. We need a little bit longer follow-up data.

It’s a very exciting area. We talk a lot to patients about this. I have to say, it’s an ongoing conversation because I’ll tell patients at the beginning of neoadjuvant therapy, when they’re finishing radiation—and I’m bringing it up for the 10th time—it’s a surprise....It’s something we have to keep talking about with our patients, because they like a neat package [at the] beginning and end of treatment, and we’re extending the targeted therapy, not just the endocrine therapy. That’s important for our patients.

Reference

Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024;390(12):1080-1091. doi:10.1056/NEJMoa2305488