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Holistic Treatment of Patients with HRpos HER2neg MBC and Comorbidities

CME

Treating the Whole Patient: Understanding Needs of Patients With HR-Positive/HER2-Negative MBC and Comorbidities

Physicians: Maximum of 0.50 AMA PRA Category 1 Credit™

Released: March 07, 2025

Expiration: September 06, 2025

Sara A. Hurvitz
Sara A. Hurvitz, MD, FACP
CME/CE Information

Activity

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Key AEs With CDK4/6 Inhibitors: Monitoring and Prevention to Maximize Adherence

As previously stated, a key AE associated with CDK4/6 inhibitors is neutropenia, which is associated with all 3 CDK4/6 inhibitors but most commonly with ribociclib and palbociclib.9-11 Complete blood counts for all patients receiving a CDK4/6 inhibitor should be performed with appropriate monitoring for neutropenia. All 3 CDK4/6 inhibitors are associated with diarrhea, but it is most commonly observed with abemaciclib. Patients should be warned about this potential AE and prepared to have antidiarrheals on hand.

Abemaciclib is also associated with a risk of VTE, thus it may not be an appropriate choice for a patient with a history of a prior VTE or at high risk of a clotting event. Because ribociclib is associated with a risk of QTc prolongation, patients should be monitored with ECGs prior to treatment initiation and every 2 weeks for the first 2 months. Concomitant medications should be carefully examined prior to starting treatment to ensure that patients at high risk of QTc prolongation are not given ribociclib.

Patients  receiving palbociclib, ribociclib, or abemaciclib need to be monitored for symptoms and signs of interstitial lung disease or pneumonitis. Hepatobiliary toxicity, including elevations in alanine aminotransaminase and aspartate aminotransferase, are more commonly associated with abemaciclib and ribociclib. Proactive management and careful monitoring of patients receiving CDK4/6 inhibitors will assist with treatment adherence and patient safety. Dose modifications as indicated in the prescribing information may be necessary to manage AEs. One might consider having patients seen by a nurse or physician when they come in for bloodwork every 2 weeks for the first 2 months of treatment with a CDK4/6 inhibitor to ensure they are tolerating treatment well and following the dosing instructions.

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Important Drug Interactions

Drug–drug interactions are a potential concern with all 3 of the CDK4/6 inhibitors. CYP3A inhibitors are contraindicated with all 3 agents, and CYP3A inducers should also be avoided. Drugs that prolong the QT interval should be avoided when administering ribociclib. CYP3A substrates should be used with caution when taken in combination with palbociclib or ribociclib.

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A 72-year-old woman presents with metastatic estrogen receptor (ER)-positive/HER2-negative breast cancer involving the liver and bones. She has a history of irritable bowel syndrome and hypertension for which she is currently receiving a diuretic agent. She also has a history of atrial fibrillation for which she takes amiodarone. She has right lower extremity deep vein thrombosis (DVT) and has completed 6 months of anticoagulation therapy. The patient has a history of depression and is currently receiving citalopram.

In your discussion with this patient with HR-positive/HER2-negative MBC and comorbid conditions who is considering a CDK4/6 inhibitor-based therapy, which of the following should be considered to achieve optimal outcomes whilst avoiding drug–drug interactions?

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