Predicting drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors and forward planning

Area of Science:

• Oncology
• Pharmacology
• Drug Interactions

Background:

• Cyclin-dependent kinase (CDK) 4/6 inhibitors are standard therapy for HR+/HER2- metastatic breast cancer.
• Their use is expanding to the adjuvant setting, increasing the importance of understanding drug-drug interactions (DDIs).

Purpose of the Study:

• To review key background information on CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib).
• To discuss significant drug-drug interactions, including those with proton pump inhibitors and CYP3A4 substrates, inhibitors, and inducers.
• To explore effects on membrane transporters and drugs increasing CDK4/6 toxicities, and to propose strategies for minimizing DDIs.

Main Methods:

• Literature review focusing on CDK4/6 inhibitors.
• Analysis of drug-drug interactions based on drug metabolism (CYP3A4) and transport.
• Examination of patient factors contributing to polypharmacy and increased DDI risk.

Main Results:

• CDK4/6 inhibitors interact with proton pump inhibitors, affecting absorption.
• Interactions with CYP3A4 substrates, inhibitors, and inducers can alter CDK4/6 metabolism.
• Certain drugs can increase the risk of CDK4/6 toxicities, particularly in older patients with comorbidities.

Conclusions:

• Mindful consideration of concomitant medications affecting absorption and metabolism is essential.
• Patient characteristics, such as polypharmacy in older adults, necessitate careful treatment planning.
• Strategies to minimize DDIs are crucial for optimizing CDK4/6 inhibitor therapy in breast cancer.