Health economic outcomes and costs of CDK4/6 inhibitor use in first- versus second-line for advanced breast cancer: A cost-effectiveness analysis of the phase 3 SONIA trial

BACKGROUND: The SONIA phase 3 trial demonstrated adding cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) to first-line endocrine therapy (aromatase-inhibitor) was not superior in terms of progression-free survival after two treatment lines compared to addition to second-line (fulvestrant) in patients with hormone-receptor positive, HER2-negative advanced breast cancer. Although critical to inform decision-making, a detailed health economic evaluation of both treatment strategies is currently lacking. METHODS: We estimated the cost-effectiveness of CDK4/6i use in first- versus second-line over 5 years using patient-level data. Quality-adjusted life-years (QALYs) were estimated using EQ-5D-5L questionnaires. Hospital resource use was collected while on SONIA treatment and cancer medications until the end of follow-up. Costs are presented in 2024 Euros. Outcomes were adjusted for censoring (data cut-off 1 December 2022) and several scenario and sensitivity analyses were conducted. RESULTS: Estimated life-years were 3.509 SE 0.075 versus 3.513 SE 0.084; difference -0.004, 95 % CI -0.232 to 0.223 in those receiving CDK4/6i in first- versus second-line, and QALYs were 2.694 SE 0.068 versus 2.644 SE 0.081; difference 0.054, 95 % CI -0.143 to 0.250, respectively. Healthcare costs were higher among patients receiving CDK4/6i in first- versus second-line (€61,821 SE 1423 versus €39,057 SE 1513; difference €22,764, 95 % CI €18,815 to €26,713). This was largely driven by higher CDK4/6i drug costs (€24,699, 95 % CI €21,833 to €27,564), with no differences in the costs of secondary care visits. The ICER was €423,408 per QALY gained. Scenario and sensitivity analyses showed similar results. CONCLUSION: Delaying CDK4/6i treatment to second-line leads to large cost savings while achieving the same patient health outcomes. TRIAL REGISTRATION: The SONIA trial was registered at ClinicalTrials.gov (NCT03425838).