A Nurse Navigator’s Perspective on CDK4/6 Inhibitors

Sharon S. Gentry, MSN, RN, HON-ONN-CG, AOCN, CBCN
Program Director, AONN+

Metastatic breast cancer (MBC) or advanced breast cancer (ABC) signifies that cancer has spread to a distant organ site, either as a progression or a recurrence after a patient has first been diagnosed with an earlier stage of breast cancer. Alternatively, in the case of de novo MBC, MBC or ABC is staged as being metastatic or stage IV at diagnosis. Mariotto and colleagues have estimated that the MBC population in the United States has been steadily increasing. Between 1990 and 2000, the prevalence increased by 4%; from 2000 to 2010, by 17%; and from 2010 to 2020, it is projected to increase by 31%.1 Their calculations using Surveillance Epidemiology and End Results data show that 40% of patients have been living with MBC for 2 years or less and 34% have lived with the disease for 5 years or more. Recurrent disease can be observed many years after initial early-stage diagnosis, with 70% of the MBC population having estrogen receptor–positive (ER+) disease.2 The American Society of Clinical Oncology guideline for MBC emphasizes the quality-of-life focus when endocrine therapy is recommended as initial treatment for patients whose disease is not immediately life-threatening or for those who are not experiencing rapid visceral recurrence during adjuvant endocrine therapy.2

An open conversation with a patient at this transition point of an MBC diagnosis should stress that, although the disease may be incurable, care can focus on control and hope as long as possible, with a balance for quality of life. In addition to providing emotional support to patients with MBC, navigators should support patient resilience by counseling individuals on how to channel their emotional roller-coaster and educating them on how treatment may be different this time versus treatment after their initial diagnosis. Patients need clarification that metastatic cancer can have very different characteristics or biomarkers from their primary cancer, and that decisions regarding systemic treatment are based on testing for these attributes. For the ER+ MBC population, the evolving landscape with multiple drugs allows many options for control. This control can be enhanced with education on the newer oral therapies, emphasis on oral adherence, and proactive teaching on tolerable side effects, as well as directing patients to resources for financial support.

The emphasis on the new generation of specific cyclin-dependent kinase (CDK)4/6 inhibitors allows the patient to see the recent progress in treating MBC via ER-signaling pathways and the hope that future developments may continue to unravel ER resistance. The primary goal of treatment is to control MBC for an indefinite period of time, and if one treatment stops working, other options are usually available. Each CDK4/6 inhibitor website has educational information for patients on the medication, and some have detailed visuals on the drug’s mechanism of action to enhance patient understanding.

Oral adherence to or compliance with CDK4/6 inhibitors is an emerging challenge in cancer care. There are no studies on CDK4/6 inhibitor adherence rates and survival, but in a retrospective cohort study, patients with breast cancer who received tamoxifen therapy with an adherence index <80% had poorer survival rates than those who were more compliant.3 Correct education on dosing is critical with CDK4/6 inhibitors, as oral administration ranges from continuously every 12 hours daily (abemaciclib) to 21 days of a 28-day cycle (palbociclib and ribociclib). Often, a second oral agent is given daily alongside the CDK4/6 inhibitor tablet or an intramuscular injection is added on days 1, 15, and 29 of the first month and then once monthly thereafter.

Nursing interventions must incorporate education on taking the medication at the same time each day, not chewing the tablets, and resuming the next dose at its scheduled time if a medication is missed. Reminder prompts such as apps, text messages, or alarms on a mobile device; written dosing trackers/calendars; or verbal reminders by another individual may assist with adherence to CDK4/6 inhibitors. Another valuable teaching point addresses that doses may be reduced if necessary due to patient intolerance and sensitivity.

Side effects that are frequently associated with CDK4/6 inhibitor therapy, such as diarrhea and neutropenia, are well-known to oncology navigators, and they understand the importance of proactive teaching to address how to report and treat these events. When teaching about diarrhea, the nurse should ask the patient to provide a definition of loose stools so the nurse and patient can reach a common definition for ongoing assessment. The nurse can then discuss methods to minimize diarrhea, such as taking antidiarrheal agents, increasing nonalcoholic fluids, limiting dairy products and raw vegetables, as well as avoiding caffeine. Neutropenia monitoring is initially started every 2 weeks for these patients. Individuals who travel long distances for care may be able to get their laboratory tests performed by a healthcare provider in their local community to decrease travel costs. Of course, the patient should always report any fever, chills, or any other signs or symptoms of infection.

Patients undergoing treatment with ribociclib should be educated on its unique side-effect profile, including abnormal heart rhythms, such as a fast or irregular heartbeat, or dizziness, which must be reported by the patient if they occur. Patients should also be instructed to tell their healthcare provider if they experience jaundice, tea-colored urine, or pain on the right side of the abdomen, all of which may indicate liver problems. Palbociclib may affect red blood cell and platelet counts, so nurses should encourage patients to share any concerns regarding dizziness, weakness, easy bleeding or bruising, or shortness of breath. Abemaciclib may also cause liver problems as well as venous thromboembolic events, and patients should report any pain or swelling in the arms or legs, shortness of breath, or chest pain.

Because patients with MBC are facing chronic disease care, financial concerns are paramount. Each CDK4/6 inhibitor website describes ways to save on drug costs and provides care teams that can reach out to patients individually to help answer insurance questions, assess for additional cost-savings, and provide further details on a specific CDK4/6 inhibitor. These websites also list national MBC advocacy groups and networks to increase patient resilience by empowering them with expert information and offering them a peer support community. Navigators often find such resources invaluable when promoting patient adherence to those challenged with the daily cost of living with their disease.

The support from company resources may be converted to navigation metrics. One measure may reflect cost-savings to the patient as they participate in the CDK4/6 patient support programs. For example, a patient may save up to $25,000 over a 12-month enrollment period on out-of-pocket expenses by enrolling in a specific drug support program. Cost-savings may also be reflected to the healthcare organization, which did not have to use benevolence or drug expense foundation programs to allow the patient to receive care.

Another measure to capture is the number of navigated patients who are referred to individual CDK4/6 inhibitor care networks per month. These support programs help patients understand what to expect when they are treated with a particular CDK4/6 inhibitor, as well as answer individual questions about the medication.

Many patients with MBC are living life to the fullest while being treated for advanced-stage disease. They continue to work full-time, raise their families, travel, and be active in their local communities. The expanding world of CDK4/6 inhibitor therapy is allowing treatment at home versus in a clinical setting, with easier, consistent dosing evolving over time. Thousands of patients need to be recognized for their participation in clinical trials to bring this drug classification to the front line of MBC care. These drugs have improved quality of life for patients with MBC, as well as extended the time they have to lead a productive life. The navigators who walk daily with the women on this journey of care appreciate their resilience during an unwanted change in their health, as well as the companies that have created programs and resources to support MBC care.


  1. Mariotto A, Etzioni R, Hurlbert M, et al. Estimation of the number of women living with metastatic breast cancer in the United States. Cancer Epidemiol Biomarkers Prev. 2017;26:809-815.
  2. Rugo HS, Rumble RB, Macrae E, et al. Endocrine therapy for hormone receptor–positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 2016;34:3069-3103.
  3. McCowan C, Shearer J, Donnan PT, et al. Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer. Br J Cancer. 2008;99:1763-1768.
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Last modified: August 10, 2023

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