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CDK4/6 Inhibitors HR Positive HER2 Negative EBC

CE

Case Challenge: Optimizing Patient–Provider Communication About CDK4/6 Inhibitors for Treatment of HR+/HER2- EBC

Physician Assistants: maximum of 1.00 hour of AAPA Category 1 CME credit

Registered Nurses: 1.00 Nursing contact hour

Released: May 22, 2026

Expiration: November 21, 2026

Ashley Martinez
Ashley Martinez, DNP, APRN, FNP-BC, AOCNP, CPHQ, NEA-BC, NPD-BC
CME/CE Information

Activity

Progress
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Course Completed

Case Conclusion
PK agreed to stay on her current treatment regimen of abemaciclib in combination with AI. She started taking an OTC antidiarrheal and made some dietary modifications that resulted in more normal bowel movements and increased energy so she can continue being active.

Key Research and Summary 

Approved CDK4/6 inhibitors for HR-Positive/HER2-Negative EBC
There are currently 2 CDK4/6 inhibitors FDA approved for patients with HR-positive/HER2-negative EBC at high risk of recurrence: abemaciclib and ribociclib. Ribociclib is approved in combination with an AI for patients with stage II-III HR-positive/HER2-negative EBC at high risk of recurrence.2 In contrast, abemaciclib plus ET is FDA-approved specifically for patients with node-positive HR-positive/HER2-negative EBC at high risk of recurrence.3

The MonarchE and NATALEE trials both report positive iDFS results when used in combination with ET or AIs.  In monarchE, after a median follow-up of 6.3 years, OS reached statistical significance, with a median OS of 86.8 months for abemaciclib plus ET compared with 85.0 months for ET alone (hazard ratio: 0.842; P = 0.0273).4 In the NATALEE trial, as OS data matured, a favorable trend continued to be observed with ribociclib plus an NSAI (hazard ratio: 0.80; 95% CI: 0.64-1.00; nominal P = .026).5 Both point to the conclusion that CDK4/6 inhibitors can avert or delay recurrence among people with ER-positive /HER2-negative disease.

However, it is important to note that adjuvant CDK4/6 inhibitors are not interchangeable, as their FDA indications and NCCN recommendations differ based on the design of their respective phase III trials (NATALEE for ribociclib and monarchE for abemaciclib).5,9

Ribociclib in combination with an AI is FDA approved for patients with stage II–III HR-positive/HER2-negative EBC at high risk of recurrence. NCCN Guidelines further recommend considering ribociclib plus an AI for patients with:

  • Node-positive disease, or
  • Node-negative disease with high-risk features (eg, tumor >5 cm; tumors 2-5 cm that are grade 2 with high genomic risk or Ki-67 ≥20%, or grade 3)2

In contrast, abemaciclib plus ET is FDA approved specifically for patients with node-positive HR-positive/HER2-negative EBC at high risk of recurrence. NCCN defines high-risk disease in this context as:

  • ≥4 positive axillary lymph nodes, or
  • 1-3 positive axillary lymph nodes with at least 1 of the following: tumor ≥5 cm or grade 3 disease1,3

When providing patient education on the approved CDK4/6 inhibitors for HR-positive/HER2-negative EBC, communicating iDFS and OS data is important and should be done in simple language that is easy to interpret by the patient. OS can be explained as the average length of time patients are alive after the start of treatment, and iDFS as the average length of time from the start of treatment that patients remain cancer free.15

Considering Patient Preference in Treatment Decisions
As shown in this case vignette, there are 2 options for CDK4/6 inhibitors for patients with EBC. It is important to have shared conversations about the potential side effects unique to each inhibitor so you can pick the best treatment tailored to your patient’s preference and lifestyle.

CDK4/6 inhibitors have AEs, but they can all be managed through supportive care, dose reductions, or treatment interruption. Patients report that HRQoL is maintained for both abemaciclib and ribociclib.7,8 Tolerability of CDK4/6 inhibitors is unique to every patient and influenced by a variety of factors such as comorbidities, lifestyle, and recurrence risk.16 Both abemaciclib and ribociclib had discontinuation rates of 18% in clinical trials.4,17 A distinct AE for abemaciclib is diarrhea. However, the incidence of grade 3-4 neutropenia with abemaciclib is lower than that seen with other CDK4/6 inhibitors. Another AE that seems to be unique to abemaciclib is an increase in serum creatinine, which generally persists for the duration of treatment. This creatinine elevation is from inhibition of renal transporters and may not reflect real kidney damage. Thus, assessment of possible kidney damage should be done with other markers like cystatin C.18 With ribociclib, there is a risk of QTc interval prolongation. It is recommended to monitor ECGs and electrolytes prior to treatment initiation, with repeat ECGs at approximately Day 14 of the first cycle, at the beginning of the second cycle, and as clinically indicated.2,3,9,10

Additional considerations:

  • Ribociclib, unlike abemaciclib, is taken on a 28-day cycle that includes 7 days off.
  • Abemaciclib can be used in conjunction with tamoxifen as the ET backbone, whereas ribociclib cannot.
  • It is recommended that patients continue treatment with abemaciclib for 2 years and ribociclib for 3 years. It is best if patients complete the full duration of treatment, even with a dose reduction, rather than discontinuing due to AEs to avoid disease recurrence or progression to metastatic disease.
  • Patients may have preferences regarding the duration of therapy. In addition, potential AEs should be carefully reviewed in the context of the patient’s medical history to ensure the selected therapy does not pose an increased risk based on known comorbidities or prior conditions.
  • It may be appropriate to conduct a cost analysis and evaluate available cost assistance or savings programs for each potential treatment option to determine the most cost-effective approach for each patient.
  • An important question that often comes up is whether the use of dose reductions to manage AEs associated with abemaciclib or ribociclib can compromise efficacy. Data from the monarchE and NATALEE trials have demonstrated that dose reduction of either of these agents does not appear to affect the iDFS benefit.13,14 It is better for patients to remain on treatment than to permanently discontinue the CDK4/6 inhibitor. Dose reductions or modifications should be used if necessary and as indicated for the management of the specific AE being experienced by the patient.

Do you plan to make any changes in your clinical practice based on what you learned in today’s program?