CDK4/6 Inhibitors Moving Into Early-Stage Breast Cancer is a “Huge Advance”

In a conversation with CancerNetwork® at the 2025 International Congress on the Future of Breast Cancer East hosted by Physicians Education Resource LLC®, Hope S. Rugo, MD, spoke about the evolving role that CDK4/6 inhibitors may play when implemented into early-stage treatment for patients with breast cancer.

Although this class of drugs may confer a risk of adverse effects and additional costs, Rugo stated that they are the “best tolerated agents” that clinicians have in this setting, as they have demonstrated reductions in the risk of distant recurrence, a key goal of oncologists. Furthermore, she noted an “incredibly exciting” carryover effect in which the risk of recurrence may decrease even years after patients stop receiving treatment with CDK4/6 inhibitors, based on reports from studies like the phase 3 monarchE trial (NCT03155997) assessing abemaciclib (Verzenio) after surgery for patients with hormone receptor–positive/HER2-negative breast cancer.

Regarding ongoing initiatives in the space, Rugo stated that additional findings are necessary to determine the optimal duration of treatment and whether the previously described carryover effect may wane over time.

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:

It’s been a huge advance that we’ve been very excited to see, moving CDK4/6 inhibitors into the early-stage setting. They are the best tolerated targeted agents that we have, although there are [adverse] effects that patients have, and we have to consider the use of these agents very carefully because we’re adding both [adverse] effects as well as cost and additional time. Patients have to come in to get blood tests, monitoring, and more frequent clinic visits. There are all sorts of things that you have to take into account when you’re adding more therapy. The biggest question we have is, what’s the benefit? We’ve already seen that there is not only a reduction in the rate of recurrence, but also the rate of distant recurrence, which is our key goal as oncologists, and that’s what the patients are focused on, as well.

Then we’ve seen that there’s a carryover effect, which is so incredibly exciting because what you see is that not only are you reducing the risk of recurrence while you’re [giving] the drug, but that even 3 years after stopping the drug, you’re seeing a significant drop in the number of patients with distant metastases from the 5-year data from the monarchE trial. We’ve seen carryover data with a ribociclib [Kisqali] trial as well, with a slightly shorter follow-up period.

We’re also seeing that suggestion of an increasing benefit over time. It’s interesting; it’s not just a carryover effect, but by [giving] the drug here early, you’re having a bigger effect later on the risk of distant recurrence. We know the risk goes out to 20 years plus for patients with hormone receptor–positive disease, so we need more time or follow-up and additional biomarkers to help us understand the optimal duration. One drug given for 2 years, one drug given for 3 years—we don’t know what the optimal duration is. We’re just going to need to longer-term follow-up to see [if] there is a time when the effect seems to wane. We’re seeing fewer patients living with metastatic disease, although we’re waiting for their survival data, but we’re hoping to see survival data from moncarchE within the next year [or less than that]. That’s also going to be highly anticipated data.

Reference

Rastogi P, O’Shaughnessy J, Martin M, et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor–positive, human epidermal growth factor receptor 2–negative, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol. 2024;42(9):987-993. doi: 10.1200/JCO.23.01994. Erratum in: J Clin Oncol. 2024;42(17):2111. doi:10.1200/JCO.24.00711. Erratum in: J Clin Oncol. 2025;43(1):113. doi:10.1200/JCO-24-02469