TOPLINE:

In a phase 3 trial-based cost-effectiveness analysis for advanced breast cancer, treatment with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in the second line rather than the first line produced similar health outcomes and reduced costs by €22,764 per patient.

METHODOLOGY:

• In this study, 1050 women (median age, 64 years) with hormone receptor-positive, HER2-negative advanced breast cancer were randomly assigned to receive either CDK4/6 inhibitors with an aromatase inhibitor in the first line, followed by fulvestrant in the second line, or an aromatase inhibitor alone followed by fulvestrant plus CDK4/6 inhibitors in the second line.
• Cost-effectiveness, a key secondary endpoint of the trial, was assessed using patient-level data up to December 1, 2022.
• Patients reported health-related quality of life using the EuroQol 5-Dimensions (EQ-5D-5L) questionnaires from the start of both first- and second-line treatments and at treatment discontinuation.
• Outcomes included life-years, quality-adjusted life-years (QALYs), healthcare costs in 2024 euros, and incremental cost-effectiveness ratio (ICER) over a 5-year period.

TAKEAWAY:

• The baseline EQ-5D questionnaire was completed by 87% of patients, 88% completed at least one follow-up questionnaire, and the overall response rate across all timepoints during follow-up was 76%, with similar rates seen between two treatment groups.
• Estimated life-years showed minimal difference between first- and second-line CDK4/6 inhibitor groups (3.509 vs 3.513; 95% CI, -0.232 to 0.223), and QALYs were comparable (2.694 vs 2.644; 95% CI, -0.143 to 0.250).
• Healthcare costs were significantly higher with first-line CDK4/6 inhibitors than with second-line CDK4/6 inhibitors (mean difference, €22,764; 95% CI, €18,815-€26,713).
• Overall, the ICER was €423,408 per QALY gained for first-line treatment with CDK4/6 inhibitors, exceeding common international willingness-to-pay thresholds.

IN PRACTICE:

"In this pre-planned trial-based cost-effectiveness analysis using the phase 3 SONIA trial, first-line CDK4/6i [CDK4/6 inhibitor] use was found not to be cost-effective compared to second-line use with the ICER of €423,408 per QALY exceeding all commonly used international willingness-to-pay thresholds," the authors wrote. "Delaying CDK4/6i treatment to second-line leads to large cost savings while achieving the same patient health outcomes," they added.

SOURCE:

This study was led by Noor Wortelboer, MD, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands. It was published online on October 25, 2025, in the European Journal of Cancer.

LIMITATIONS:

Given the median follow-up duration of approximately 3 years and the maximum follow-up duration of 5 years, the authors applied a 5-year time horizon, despite health economic guidelines often arguing for a lifetime horizon. Second-line treatment started at different timepoints for each patient. The analysis was restricted to healthcare costs. Additionally, this study was conducted in a Dutch setting, limiting generalisability.

DISCLOSURES:

The trial was sponsored by the Dutch Breast Cancer Research Group and received funding from the Netherlands Organization for Health Research and Development and Dutch health insurance companies. Five authors reported receiving grants and consulting fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.