The Case of the CDK4/6 Inhibitors Checklist
Three years ago, Sarah, age 54, completed standard chemotherapy and radiation treatment for stage II, ER- and PR-positive, HER2-negative invasive breast cancer. A recent computed tomography scan, ordered to evaluate persistent hip pain, revealed bone lesions, and a biopsy and positron-emission tomography scan confirmed bone-only metastatic breast cancer. A CDK4/6 inhibitor, ribociclib, was added to the letrozole she was already taking.
Sarah tells the oncology nurse that she has been experiencing mild nausea with the ribociclib and asks if she can take ondansetron that she still has from when she was on chemotherapy. She also questions why the oncologist chose ribociclib and why the fentanyl patch she was using to control pain was changed.
What Would You Do?
CDK4/6 inhibitors act by suppressing specific proteins involved in regulating cell cycle division. Each of the three U.S. Food and Drug Administration-approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are used in combination with endocrine therapy (aromatase inhibitors or fulvestrant). Abemaciclib, the most potent of the CDK4/6 inhibitors, is also approved for use as a single agent in pretreated patients (https://doi.org/10.1038/s41523-019-0121-y). Despite sharing the same drug class and mechanism of action, each of the CDK4/6 inhibitors has unique dosing, administration, and side-effect profiles. Additionally, some comorbidities may prohibit patients’ use of one or more drugs in this class of medication (https://doi.org/10.2174/1568009617666170330120452).
Side effects common to CDK4/6 inhibitors include fatigue, nausea, diarrhea, and neutropenia. Uncomplicated prolonged QT interval is associated with ribociclib, so baseline and periodic electrocardiograms and electrolyte monitoring are part of the treatment plan (https://www.ons.org/clinical-practice-resources/hr-metastatic-breast-cancer-targeted-therapy-profiles). Several food-drug and drug-drug interactions are associated with CDK4/6 inhibitors. Because CDK4/6 inhibitors are metabolized via the CYP3A pathway, patients should avoid grapefruit and pomegranate products and medications that interact with the CYP3A pathway.
Fentanyl is a CYP3A substrate with a narrow therapeutic index; concomitant use with CDK4/6 inhibitors could affect QT prolongation and requires close monitoring and potential dosage adjustments. Serotonin (5-HT3) antagonists (ondansetron, granisetron, or palonosetron) can also affect QT prolongation (https://doi.org/10.1007/s11912-019-0769-3).
Sarah’s nurse explains that oncologists consider patients’ overall health when deciding which CDK4/6 inhibitor to prescribe. The nurse also educates Sarah regarding the CYP3A system and what foods and drugs, including fentanyl and ondansetron, can interact with CDK4/6 inhibitors. She encourages Sarah to discuss an alternative antiemetic with her oncologist and to dispose of expired medications.
To learn more about CDK4/6 inhibitors and earn nursing continuing professional development credits, visit the ONS website (http://www.ons.org/courses/cdk46-inhibitor-case-study-series-bundle).