Adjuvant Ribociclib and Abemaciclib in Early HR+ Breast Cancer (Full Video)
Key Points
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The CDK4/6 inhibitors, abemaciclib and ribociclib, have both improved outcomes for patients with hormone receptor (HR)-positive, HER2-negative early breast cancer.
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Abemaciclib has slightly more mature follow-up data from the monarchE trial and has recently shown an overall survival (OS) benefit.
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Ribociclib has broader eligibility criteria than abemaciclib; otherwise, selecting between the two agents should be a shared decision with the patient based on their distinct side effect profiles.
Adjuvant CDK4/6 Inhibitors in HR+ Early Breast Cancer
At the 2025 San Antonio Breast Cancer Symposium, cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Center, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, discussed CDK4/6 inhibitors in patients with HR-positive, HER2-negative early breast cancer with three breast cancer experts. Two standard CDK4/6 inhibitors, abemaciclib and ribociclib, were evaluated in the monarchE and NATALEE trials, respectively.
NATALEE and monarchE Trials
The phase 3 NATALEE trial enrolled patients with stage II HR-positive early breast cancer to receive ribociclib 400 mg plus non-steroidal aromatase inhibitor (NSAI) or NSAI alone. NATALEE enrolled patients with stage III disease, stage IIB disease, or stage IIA plus N1 disease. T2N0 patients were also eligible if they had grade 3 disease or grade 2 disease with another high-risk genomic feature. The trial reported that the addition of ribociclib to NSAI significantly improved invasive disease-free survival (DFS) and distant DFS.
In node-negative patients, the risk versus benefit of additional CDK4/6 inhibitor therapy was unclear given the increased toxicity and treatment burden. However, recent follow-up data from NATALEE showed a continued benefit in this setting. “Having that data in the lymph node-negative [population] and really showing that significant improvement there is really helpful as we counsel patients and think about how to approach treatment,” said Eleonora Teplinsky, MD, of Valley Health System.
Compared with NATALEE, monarchE had stricter eligibility criteria, only enrolling patients with 4 positive axillary lymph nodes or with 3 positive nodes plus grade 3 disease or tumor size of 5 cm or greater. The monarchE data update at the 2025 European Society of Medical Oncology Congress showed that the addition of abemaciclib improved OS compared with endocrine therapy alone.
CDK4/6 Inhibitor Side Effects
Of these two CDK4/6 inhibitors, abemaciclib is most commonly associated with diarrhea, while ribociclib is typically associated with lower gastrointestinal toxicity but is more frequently associated with cytopenias, liver enzyme elevations, and QTc interval prolongation. To manage toxicity, complete blood counts to monitor for cytopenias should be performed every 2 weeks for the first 2 months, every month for the next 2 months, and then as indicated every 2 or 3 months thereafter.
For ribociclib, EKG testing should be performed at the 2-week mark, but repeat testing is not needed if the QTc interval is normal. Oncologists should also ensure patients are not on other medications that can prolong the QTc interval. Liver enzyme elevations may be managed with dose holds or reductions, though there are some emerging data on the use of steroids to manage higher-grade events.
For abemaciclib, the TRADE study showed that a dose escalation strategy reduced the rate of discontinuation or inability to reach or maintain the full 150 mg dose. “I now start most of my patients at 100 mg and ramp up if I’m able to,” said Sherry Shen, MD, of Memorial Sloan Kettering Cancer Center.
Choosing Ribociclib or Abemaciclib
The panel discussed what factors guide the decision between abemaciclib and ribociclib. A proportion of patients will only be eligible for ribociclib based on the broader inclusion criteria from NATALEE. For patients eligible for both abemaciclib and ribociclib, the panel agreed that selection primarily comes down to which CDK4/6 inhibitor has a more appropriate side effect profile based on the individual patient’s goals, concurrent medications, and comorbidities. Generally, the diarrhea associated with abemaciclib can be very disruptive to daily activities, and ribociclib can feel more tolerable from the patient’s perspective, said Dr. Shen.
If toxicities are unmanageable with either abemaciclib or ribociclib, swapping to the other may be successful. However, there are currently no data to answer whether the planned treatment duration for the new agent should be adjusted based on the duration of treatment already completed with the previous agent.
Some oncologists lean toward abemaciclib based on the published OS benefit, but as NATALEE data mature to the point that monarchE data has, both agents are likely to show a substantial carryover benefit, said Sara Hurvitz, MD, FACP, of Fred Hutchinson Cancer Center.
“We are just beginning to appreciate the benefit of these agents in our highest risk patients… I think these data are going to continue to evolve, but it’s so great for us to have this tool in our armamentarium, the trick is helping our patients tolerate it long-term,” said Dr. Hurvitz.