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September 10, 2025

First-line cyclin-dependent kinase 4 and 6 inhibitors in combination with an aromatase inhibitor for HR+/HER2- metastatic breast cancer: A real-world cost-effectiveness assessment in a US Medicare-eligible population

Key Points

Projected life expectancy with CDK4/6 inhibitors is similar for palbociclib, ribociclib, and abemaciclib, indicating treatment equivalence.
Total lifetime health care costs for patients aged 65 and older receiving palbociclib, ribociclib, or abemaciclib are comparable, at about $865,000.
Real-world evidence using the Flatiron Health Analytic Database provides a novel analysis of treatment in a Medicare-eligible population.
Sensitivity analyses confirm the robustness of findings, highlighting no significant differences in cost or life expectancy across treatment options.

Abstract

In hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC), cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) in combination with an aromatase inhibitor (AI) are the preferred first-line (1L) treatment. Although prior cost-effectiveness models comparing CDK4/6is palbociclib, ribociclib, and abemaciclib have used data from placebo-controlled clinical trials, no analyses in the United States have been conducted using real-world evidence (RWE) for a US Medicare-eligible population. To estimate the long-term clinical outcomes and health care costs of 1L CDK4/6i treatment in patients aged 65 years and older using RWE. We developed a partitioned survival model to project patient time in progression-free and progressed disease health states. Progression-free survival (PFS) and overall survival (OS) curves for palbociclib + AI were obtained from an analysis of patients aged 65 years and older treated 1L for HR+/HER2- mBC using the Flatiron Health Analytic Database (Flatiron). Adjusted comparative effectiveness estimates vs palbociclib + AI for both ribociclib + AI (PFS hazard ratio = 0. 98 95% CI = 0. 86-1. 13; OS hazard ratio = 1. 01 95% CI: 0. 87-1. 18) and abemaciclib + AI (PFS hazard ratio = 0. 99 95% CI = 0. 86-1. 15; OS hazard ratio = 1. 00 95% CI = 0. 84-1. 19) were obtained from the same analysis. All-cause medical costs and CDK4/6i drug costs were based on an analysis of patients aged 65 years and older in Optum Clinformatics DataMart. We used a Medicare perspective over a lifetime horizon for a cohort of patients with mean age of 73. 7 years. Sensitivity analyses were performed to assess the robustness of results to plausible variation in input values. Projected life-years (LYs) with palbociclib + AI, ribociclib + AI, and abemaciclib + AI were similar: 5. 16 (95% credible range CR = 4. 94-5. 35), 5. 12 (95% CR = 4. 53-5. 82), and 5. 16 (95% CR = 4. 49-5. 90), respectively. Total lifetime health care costs were also similar (865, 000 95% CR = 807, 400-925, 000, 866, 800 95% CR = 786, 000-965, 000, and 901, 000 95% CR = 809, 000-1, 004, 600, respectively). Sensitivity analyses further supported no differences in LYs or total costs between CDK4/6is. Based on effectiveness and cost estimates from real-world data, our analyses suggest that palbociclib, ribociclib, and abemaciclib produce similar life expectancy and health care costs in US patients aged 65 years and older with HR+/HER2- mBC.

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