Abstract / Summary
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have transformed the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) breast cancer. Ribociclib plus an aromatase inhibitor (AI) was approved in Canada as adjuvant treatment for high-risk stage II–III early breast cancer (EBC) based on the phase 3 NATALEE trial, demonstrating improved invasive disease-free survival (iDFS) versus AI treatment alone. This study evaluated the cost-effectiveness of ribociclib plus AI versus AI alone and tamoxifen from a Canadian public payer perspective. A non-homogeneous, semi-Markov cohort model with six health states (iDFS, second primary malignancy, non-metastatic recurrence, remission, distant recurrence [DR], and death) was developed, using Ontario-based costs (Canadian dollars) and a lifetime horizon. Transition probabilities from iDFS were derived from NATALEE trial data; other transitions were informed by published sources. DR was stratified by endocrine therapy (ET) sensitivity based on recurrence timing (≤ 12 months post-ET: resistant; > 12 months: sensitive), with outcomes and costs informed by prior health technology assessment evidence in metastatic disease. Results were reported as incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained. Ribociclib plus AI yielded a probabilistic ICER of $45,097/QALY versus AI alone; tamoxifen was dominated by AI alone. Sensitivity analyses showed results were most sensitive to iDFS hazard rates and ribociclib drug costs. In the probabilistic analysis, ribociclib was preferred in 58.5% of simulations at a $50,000 willingness-to-pay threshold. Ribociclib plus AI is cost-effective for HR+/HER2− EBC with an ICER of $45,097, below the $50,000 willingness-to-pay threshold versus AI or tamoxifen alone.