Powerful New Evidence Finds CDK4/6 Inhibitors Reduce Recurrence Risk In The Largest Sub-Group of Breast Cancer Patients

The ESMO discussion summarizes years of follow-up from the pivotal trials. In monarchE, adding abemaciclib to endocrine therapy in high-risk, HR-positive/HER2-negative early breast cancer continues to reduce the chance of cancer coming back and, importantly, now shows a statistically significant improvement in overall survival (living longer) compared with endocrine therapy alone. Several oncology outlets report about a ~16% reduction in the risk of death at this longer follow-up, with no new safety problems identified. That means the benefit persisted long after the two-year course of abemaciclib ended.

In NATALEE, the 5-year analysis continues to show that adding ribociclib lowered the risk of invasive disease-free events (that is, the cancer returning or a new invasive cancer developing) across a broader early-breast-cancer population than earlier CDK4/6 studies enrolled. Overall-survival data in NATALEE are still developing, but the long-term trend in delaying recurrence remains reassuring.

“I think that this will cement the role of CDK four six inhibitors in the adjuvant (after initial treatment with surgery) setting, says Dr. Sheheryar Kabraji from Roswell Park Center. I think that if we compare this to the NATALIE data, which is the use of ribociclib for three years, those data suggested that there was continued event-free survival benefit, no difference now in the overall survival seen yet, but a trend towards that there was also evidence that the node negative population seemed to benefit as much as the node positive population in the NATALIE trial.”

For patients, this matters because preventing a distant recurrence is what ultimately saves lives: the longer people stay cancer-free after surgery, the better their chances. The ESMO Daily Reporter framed these updates simply: multi-year follow-up from monarchE and NATALEE reinforces that adjuvant CDK4/6 inhibitors can provide durable protection against relapse when added to endocrine therapy in the right patients.

So… Do I Need a CDK4/6 Inhibitor?

Not everyone needs a CDK4/6 inhibitor after surgery. The trials targeted patients at higher risk of recurrence—and that’s where doctors see the biggest payoff.

• In monarchE, “high risk” generally meant larger tumors and/or cancer in multiple lymph nodes, sometimes with other aggressive features. Those patients gained a clear, lasting benefit from abemaciclib added to endocrine therapy.
• NATALEE enrolled a wider range of early breast cancers, including some patients with lower-volume node-positive or selected node-negative disease considered at enough risk to justify additional therapy. Its 5-year report shows a consistently lower chance of recurrence with ribociclib plus endocrine therapy across its prespecified groups.
  More studies are starting to estimate how many patients actually meet these trial criteria. One large analysis suggests roughly 1 in 5 women with ER-positive/HER2-negative breast cancer could meet either monarchE or NATALEE eligibility (criteria differ, and some patients meet both). Clinicians still need to individualize decisions within those broad categories.

Could this change practice?

The short answer from ESMO 2025 experts and the current state of the art is yes, especially for clearly high-risk patients after surgery (as discussed above). Long-term monarchE results showing fewer deaths with abemaciclib plus endocrine therapy are the kind of data that shift guidelines and everyday conversations. NATALEE’s 5-year results support using ribociclib in a broader early-breast-cancer population to keep recurrences at bay while we await fuller survival follow-up. Together, these updates help clinicians refine who should be offered adjuvant CDK4/6 therapy and for how long.

What does this mean if you’re deciding now?

If you’ve had surgery for HR-positive/HER2-negative breast cancer, ask your oncologist to walk through your personal risk of recurrence and whether you meet the kinds of criteria used in monarchE or NATALEE. Then ask:

• How much could this lower my risk of the cancer coming back?
• What are the side effects we’ll watch for, and how do we manage them?
• How long would I take the medicine, and how often are blood tests or EKGs needed?
• Given the new long-term data, do you think this changes the balance of pros and cons for someone like me?
• These are the exact conversations ESMO 2025 is prompting around the world: use long-term data to focus the benefit where it’s strongest, and make sure treatment plans align with each patient’s values and life.

During her talk at ESMO 2025 – paper session, Dr Angela DeMichele from the University of Pennsylvania, Philadelphia, PA, USA, reassured that “it is a very exciting time, and this area will continue to evolve rapidly.”

How To Choose Between The Available CDK4/6 Inhibitors- Personalized Decision Making

“The class of drugs, we don’t have any head-to-head data. And so we really end up choosing based on side effect profile at the current time, says the noted breast cancer specialist Dr. Hal Burstein from The Dana Farber Cancer Institute.  Ribociclib is more likely to be associated with liver function test abnormalities. Rare QTC prolongations low blood counts fatigue and requires three years of treatment and abemaciclib requires two years of treatment, but often causes more in the way of lower issues, crampy abdominal pain or diarrhea. And many patients will hear these kinds of numbers or risks and they’ll be very capable of saying, okay, well I want to try this one or that one. And we usually respect the patient preference based on the side effect profile.”

Dr. Burstein is sensitive to the fact that even within their basic treatment goals, women have different needs that can influence decision making.

“A lot of patients, especially busy active, often working women, the last thing they want is to interrupt their professional workday, whether they’re a teacher or a police officer or a lawyer or whatever they do and be racing to the bathroom or even if they just have to be responsible for their families and households, that’s not a convenient thing. At the same time, there are patients in each group who tolerate each of these drugs really well. It’s unbelievably unpredictable who’s going to have an easy time and who’s going to have a more challenging time with these drugs. And so you do have to work with patients, monitor their tolerability, monitor their blood work and other labs and see how things play out.”

 

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