Breast cancer (BC) is the most common malignancy globally, with HR+/HER2- BC accounting for approximately 70% of cases. While endocrine therapy (ET) is the foundation of treatment, resistance inevitably develops. CDK4/6 inhibitors improve overall survival when combined with ET, but further treatment options are needed upon progression. Sequential single-agent chemotherapy is a common subsequent approach, but it has limitations, including declining response rates and increased side effects. Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, has shown clinical benefit and safety in patients with HR+/HER2- metastatic BC progressing after ET and prior chemotherapy. However, its high cost raises concerns about accessibility. This study addresses this by performing a cost-effectiveness analysis of SG compared to single-agent chemotherapy for HR+/HER2- metastatic BC from a US third-party payer perspective, aiming to provide crucial information for healthcare decisions.

The introduction extensively reviews the epidemiology of breast cancer, highlighting its global prevalence and the significance of HR+/HER2- subtype. Existing treatment options are discussed, focusing on the limitations of sequential chemotherapy following endocrine therapy resistance. The literature establishes the clinical efficacy and safety of SG, while also acknowledging the substantial cost increase associated with its use compared to conventional chemotherapy. Several studies on cost-effectiveness of other treatments for HR-positive, HER2-negative metastatic breast cancer are cited to position this research within the broader economic landscape of breast cancer care. The lack of prior economic evaluation for SG in this specific context is emphasized to justify the need for this study.

This cost-effectiveness analysis employed a partitioned survival model, a method that is well-suited for evaluating treatments with prolonged survival outcomes. The model used data from the TROPiCS-02 clinical trial, which investigated SG in HR+/HER2- metastatic breast cancer patients who progressed after ET and chemotherapy. The model included three mutually exclusive health states: progression-free survival (PFS), progressed disease (PD), and death. Progression-free and overall survival curves from the TROPiCS-02 trial were digitized and fitted with appropriate parametric survival functions. Cost inputs included drug costs obtained from public databases, terminal care costs, disease management costs (including imaging and supportive care), and costs of managing grade 3 or higher adverse events (AEs), obtained from the literature. Utility values were derived from other published studies as the TROPiCS-02 trial did not report utility data. The model calculated incremental cost-effectiveness ratios (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB), comparing SG to chemotherapy. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of the model results, with key variables such as SG price and patient body weight being varied. Subgroup analyses were also conducted to explore the cost-effectiveness across different patient characteristics defined in the TROPiCS-02 trial.

The base-case analysis revealed that SG treatment resulted in an increase of 0.284 life-years and 0.217 QALYs compared to chemotherapy, at an incremental cost of $132,689. This translates to an ICER of $612,772/QALY. The INHB was -0.668 QALYs, and the INMB was -$100,208 at a willingness-to-pay (WTP) threshold of $150,000/QALY. These results indicate that SG was not cost-effective at the standard WTP threshold. Sensitivity analyses highlighted that the model's results were most sensitive to the hazard ratios for overall survival and progression-free survival, average patient body weight, and the cost of SG. Specifically, SG demonstrated cost-effectiveness at a WTP threshold of $150,000/QALY only if the price of SG was below $3.997/mg or the average patient weight was under 19.88 kg. Probabilistic sensitivity analysis generated a cost-effectiveness acceptability curve showing that at a WTP threshold of $150,000/QALY, there was no probability of SG being cost-effective compared to chemotherapy. Subgroup analyses across 22 subgroups defined in the TROPiCS-02 trial consistently showed negative INHBs for SG, indicating a lack of cost-effectiveness across all subgroups at the $150,000/QALY WTP threshold.

This study provides the first economic evaluation of SG for HR+/HER2- metastatic BC, filling a critical gap in the literature. The findings demonstrate that although SG offers clinically significant benefits in terms of survival, its high cost presents a significant barrier to cost-effectiveness from a US third-party payer perspective. The sensitivity analyses identified SG pricing as the most impactful factor on cost-effectiveness. The robustness of the model is supported by both one-way and probabilistic sensitivity analyses. The consistency of negative INHBs across all subgroups further strengthens the conclusion that SG is not cost-effective at current pricing levels. The study's findings are consistent with economic evaluations of other expensive antibody-drug conjugates, suggesting that strategies to reduce drug costs or provide financial assistance may be necessary to ensure access to these innovative treatments.

The study concludes that sacituzumab govitecan is not cost-effective for treating previously treated HR+/HER2- metastatic breast cancer at its current price. Significant price reductions are necessary to improve cost-effectiveness. Future research should consider head-to-head comparisons with other antibody-drug conjugates and explore strategies to optimize treatment selection based on individual patient characteristics.

This study has several limitations. First, the absence of head-to-head trials comparing SG to other antibody-drug conjugates limits the generalizability of the findings. Second, extrapolation of survival data beyond the observed time in the TROPiCS-02 trial introduces uncertainty. Third, the exclusion of follow-up costs might underestimate the overall cost. Fourth, the exclusion of grade 1 and 2 AEs could have led to overestimation of the economic benefits of SG. However, sensitivity analysis indicated these limitations were unlikely to materially change the study's conclusions.