Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/ human epidermal growth factor receptor 2-negative metastatic breast cancer

The study addresses whether sacituzumab govitecan (SG), an antibody–drug conjugate targeting Trop-2, is a cost-effective option versus single-agent chemotherapy for patients with hormone receptor–positive, HER2-negative metastatic breast cancer (HR+/HER2- mBC) who have developed endocrine resistance. Breast cancer is the most common cancer globally, with HR+/HER2- being the predominant subtype. Standard care relies on endocrine therapy and combinations such as CDK4/6 inhibitors, but resistance inevitably emerges, after which sequential chemotherapy is used with diminishing benefit and notable toxicity. SG has shown clinical benefit and safety in HR+/HER2- mBC post-endocrine and prior chemotherapy, but its high price raises concerns regarding affordability and value. The purpose of this study is to evaluate the cost-effectiveness of SG compared with physician’s-choice chemotherapy from a U.S. third-party payer perspective, to inform clinicians and policymakers about the economic value of adopting SG in this setting.

Background literature highlights that approximately 70% of breast cancers are HR+/HER2-, for which endocrine therapy is foundational until resistance develops. Combining endocrine therapy with CDK4/6 inhibitors improves overall survival, and other targeted combinations (e.g., PI3K or mTOR inhibitors) can provide benefit, but resistance eventually arises, leaving chemotherapy as the next option with limited efficacy and increased toxicity. Trop-2 is highly expressed in many breast cancers and is associated with progression and prognosis. SG (anti–Trop-2 linked to SN-38) leverages a bystander effect and has demonstrated clinical benefit and safety in HR+/HER2- mBC after endocrine therapy and prior chemotherapy. However, antibody–drug conjugates are costly to develop and purchase, and prior evaluations often find them not cost-effective. Before this study, SG’s economic value in HR+/HER2- mBC had not been assessed, representing an evidence gap in health economic evaluations for this patient population.

Design: Cost-effectiveness analysis using a partitioned survival model with three mutually exclusive health states: progression-free survival (PFS), progressed disease (PD), and death; 1-week cycle length. Perspective: U.S. third-party payer. Population: Hypothetical cohort reflecting TROPiCS-02 trial patients with endocrine-resistant HR+/HER2- mBC receiving SG or single-agent chemotherapy. Clinical inputs: PFS and overall survival (OS) curves sourced from TROPiCS-02; individual patient data approximated by digitizing published Kaplan–Meier curves (GetData Graph Digitizer v2.26) and reconstructing data following Guyot et al. Parametric survival models were fitted (chosen by lowest AIC/BIC). Final selected models: for SG, OS log-logistic (γ=1.9025, λ=0.0162), PFS log-normal (μ=3.1013, σ=1.0541); for chemotherapy, OS log-logistic (γ=1.9082, λ=0.0188), PFS log-normal (μ=2.7297, σ=0.9475). Model validation compared modeled PFS/OS to trial KM data. Costs: Included drug acquisition (SG, eribulin, vinorelbine, gemcitabine, capecitabine from public sources), administration, disease management/monitoring (e.g., CT scans), best supportive care, terminal care ($21,501 per metastatic BC patient), and management of grade ≥3 adverse events based on published sources. Dosing assumptions used average U.S. patient weight 74 kg and body surface area 1.82 m² for dose calculations. Costs were reported in 2023 U.S. dollars; medical care inflation applied. Utilities: Health state utilities for metastatic BC taken from literature due to lack of trial utilities: PFS=0.830, PD=0.443; death=0. Disutilities for grade ≥3 AEs incorporated from literature. Analysis: Base-case outcomes included total costs, life-years (LYs), QALYs, incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). WTP threshold set at $150,000/QALY; costs and utilities discounted at 3% annually. Sensitivity analyses: One-way sensitivity analyses varied parameters by reported 95% CIs or ±25% when unavailable. Probabilistic sensitivity analysis (PSA) used 10,000 Monte Carlo iterations with gamma distributions for costs and beta for probabilities/proportions to construct cost-effectiveness acceptability curves. Subgroup analyses varied PFS hazard ratios according to TROPiCS-02 prespecified subgroups. Software: R v4.0.5 with hesim and heemod packages. Reporting followed CHEERS 2022 guidelines.

- Base case: Compared with chemotherapy, SG increased LYs by 0.284 and QALYs by 0.217, with an incremental cost of $132,689, yielding an ICER of $612,772 per QALY. INHB was -0.668 QALYs and INMB was -$100,208 at a $150,000/QALY WTP. - Sensitivity: Results were most sensitive to hazard ratios for OS and PFS, average body weight, and SG cost. Threshold analyses indicated SG would be cost-effective at a WTP of $150,000/QALY if the SG price were below $3.997/mg (or below $2.821/mg at $100,000/QALY) or if patient body weight were under 19.88 kg. - Probabilistic analysis: At a $150,000/QALY WTP, SG had essentially no probability of being cost-effective relative to chemotherapy; probability of cost-effectiveness increased only at higher WTP levels. - Subgroups: Across all prespecified subgroups (e.g., visceral metastasis status, prior endocrine therapy duration, age, race, ECOG status, region, prior CDK inhibitor duration, investigator’s choice of chemotherapy, early relapse, number of prior chemotherapies), SG did not achieve cost-effectiveness at $150,000/QALY, with negative INHBs throughout.

The analysis directly addresses whether SG offers economic value over chemotherapy for HR+/HER2- metastatic breast cancer in the U.S. Despite clinically meaningful gains in survival endpoints, SG’s high acquisition cost leads to an ICER far exceeding conventional WTP thresholds, indicating it is not cost-effective under current pricing. Sensitivity analyses show that outcomes are driven predominantly by survival hazard ratios, patient body weight (which determines dose), and SG price, underscoring that substantial price reductions or dosing strategies that lower drug consumption would be required to improve value. The findings align with broader observations that antibody–drug conjugates, while effective, often have prices that challenge cost-effectiveness. Policy efforts to reduce drug prices and targeted financial assistance could improve access. The subgroup findings suggest that even in populations with greater clinical benefit, current pricing prevents SG from being cost-effective, highlighting the central role of drug cost. Overall, the study provides timely evidence to guide clinicians and payers on the economic implications of adopting SG in this setting.

From a U.S. third-party payer perspective, sacituzumab govitecan is unlikely to be a cost-effective option for previously treated HR+/HER2- metastatic breast cancer at standard WTP thresholds, despite clinical advantages over chemotherapy. Economic outcomes may improve through substantial price reductions and tailoring treatment to patient characteristics that reduce drug use. Future research should include head-to-head economic comparisons with other antibody–drug conjugates, incorporation of direct utility data when available, and updates as longer-term survival and resource-use data emerge.

- No head-to-head comparisons versus other antibody–drug conjugates (e.g., trastuzumab emtansine, trastuzumab deruxtecan); results should be updated when such data are available. - Survival beyond observed follow-up was extrapolated using parametric models fitted to TROPiCS-02 KM curves, introducing uncertainty in long-term outcomes. - Follow-up resource utilization costs could not be fully incorporated due to lack of time-series data. - Costs and disutilities associated with grade 1–2 adverse events were not included, potentially overestimating SG’s economic outcomes; however, one-way sensitivity analyses suggested AE cost inputs (aside from SG cost) had limited influence on results.