Background CDK4/6 inhibitors have shown promising results for treating advanced breast cancer (ABC) and are routinely used in Singapore. In view of their high costs, it is important to assess their relative value compared to existing standards of care in the local setting. Aims This study evaluates the cost‐effectiveness of adding ribociclib to goserelin and a nonsteroidal aromatase inhibitor or tamoxifen as initial therapy for premenopausal women with hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2−) ABC in Singapore. Methods A partitioned survival model with four health states (progression‐free on first‐line treatment, progression‐free on second‐line treatment, progressed disease, and death) was developed from a healthcare system perspective over a 10‐year time horizon. Key clinical inputs were derived from the MONALEESA‐7 trial, and survival curves were extrapolated beyond the trial period. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. A discount rate of 3% was applied to both costs and outcomes. One‐way deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties. Results The base‐case analysis resulted in an incremental cost‐effectiveness ratio (ICER) of SGD197, 667 per quality‐adjusted life‐year. Sensitivity analyses showed that the ICER was sensitive to the survival parametric distribution, ribociclib price, time horizon, and utility weights used. Even when these were varied, ICERs remained high and not cost‐effective in the local context. Conclusion At its current price, adding ribociclib to endocrine therapy is unlikely to be cost‐effective in Singapore for HR+, HER2− ABC. Results from this study are useful to inform future funding decisions for CDK4/6 inhibitors alongside other factors including clinical effectiveness, safety, and budget impact considerations.

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