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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Integration of pre‑existing cardiovascular comorbidity into CDK4/6 inhibitor selection for breast cancer
Chanhyun Park1, Kiyoung Kim2, Nora B Abifaraj2
1College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA.
Insights
Ribociclib is more often prescribed for breast cancer patients with hypertension, despite its higher cardiovascular risks compared to palbociclib and abemaciclib. Tailoring CDK4/6 inhibitor selection based on cardiovascular risk may prevent adverse events.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors vary in cardiovascular (CV) safety profiles.
- Ribociclib is associated with a greater risk of CV adverse events than palbociclib and abemaciclib.
Purpose of the Study:
- To investigate CDK4/6 inhibitor prescribing patterns in breast cancer patients with pre-existing cardiovascular disease (CVD) or cardiometabolic conditions.
- To assess the association between hypertension, hyperlipidemia, diabetes, and the choice of CDK4/6 inhibitor.
Main Methods:
- Retrospective cohort study utilizing 2017-2021 Merative MarketScan claims data.
- Identified women aged 18+ with breast cancer initiating a first CDK4/6 inhibitor.
- Multinomial logistic regression analyzed odds of initiating palbociclib or abemaciclib versus ribociclib, adjusting for CVD and cardiometabolic risk factors.
Main Results:
- Among 5002 patients, no risk factor significantly influenced drug choice in unadjusted analyses.
- Hypertension was associated with significantly lower odds of initiating palbociclib (AOR 0.67) and abemaciclib (AOR 0.60) compared to ribociclib.
- Pre-existing CVD, hyperlipidemia, and diabetes were not significantly associated with CDK4/6 inhibitor selection.
Conclusions:
- Ribociclib is disproportionately prescribed to breast cancer patients with hypertension, despite its CV safety concerns.
- Current CDK4/6 inhibitor selection may not adequately account for patient cardiovascular risk.
- Integrating CV risk prediction into treatment decisions could mitigate potential CV complications.
Background:
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors differ in cardiovascular (CV) safety. Ribociclib has been associated with a higher risk of CV adverse events compared to palbociclib and abemaciclib.
Objectives:
We examined patterns of CDK4/6 inhibitor selection among patients with breast cancer who had pre-existing cardiovascular disease (CVD) or cardiometabolic conditions (hypertension, hyperlipidemia, or diabetes).
Design:
We conducted a retrospective cohort study.
Methods:
Using 2017-2021 Merative MarketScan claims, we identified women ⩾18 years with breast cancer who initiated a first CDK4/6 inhibitor. The outcome was the type of CDK4/6 inhibitor. Primary factors were preexisting CVD and cardiometabolic risk factors measured in the prior 12 months. Multinomial logistic regression estimated unadjusted and adjusted odds of initiating palbociclib or abemaciclib versus ribociclib.
Results:
Among 5002 initiators (palbociclib n = 3734; ribociclib n = 328; abemaciclib n = 940), no risk factor significantly affected drug choice in unadjusted analyses; hypertension showed a non-significant trend toward lower initiation of palbociclib (odds ratio (OR) 0.94; 95% confidence interval (CI) = 0.75-1.18) and abemaciclib (OR 0.78; 95% CI = 0.60-1.00). After controlling for additional variables, hypertension was associated with 33% lower odds of initiating palbociclib (adjusted odds ratio (AOR) 0.67; 95% CI = 0.51-0.87) and 40% lower odds of initiating abemaciclib (AOR 0.60; 95% CI = 0.45-0.81) relative to ribociclib. Pre-existing CVD, hyperlipidemia, and diabetes were not associated with CDK4/6 inhibitor selection.
Conclusion:
Despite its potential higher risk of CV adverse events, ribociclib is more frequently prescribed to patients with breast cancer who have hypertension. Incorporating CV risk prediction into CDK4/6 inhibitor selection could help prevent costly CV complications.
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