Methods for Estimating Long-Term Outcomes for Trastuzumab Deruxtecan in HER2-Positive Unresectable or Metastatic Breast Cancer After Two or More Anti-HER2 Therapies.

BACKGROUND: DESTINY-Breast01 (NCT03248492) is a phase II single-arm trial evaluating trastuzumab deruxtecan (T-DXd) in adults with human epidermal growth factor receptor 2-positive (HER2+) unresectable or metastatic breast cancer (u/mBC) who have received two or more prior anti-HER2 therapies. OBJECTIVES: Objectives were to explore approaches for estimating long-term overall survival (OS) with T-DXd from immature data (June 2020 data-cut; median follow-up 20.5 months), and compare predicted long-term outcomes with UK-recommended non-targeted therapies eribulin, capecitabine, and vinorelbine. METHODS: Two methods were used to model T-DXd long-term OS: (1) applying a hazard ratio (HR) to the OS curve for another HER2 targeted therapy (third-line trastuzumab emtansine [T-DM1]) with longer trial follow-up; and (2) extrapolating T-DXd OS data directly. Comparator OS was based on direct extrapolation of published data (comparison with vinorelbine OS was not possible). Quality-adjusted life years (QALYs) were calculated using a previously published model of utility. RESULTS: Both extrapolation methods demonstrated longer mean/median OS with T-DXd versus eribulin, and capecitabine (44.7/32.9 months [applying an HR to the T-DM1 OS curve]; 47.7/29.9 months [using direct extrapolation]; vs 11.3/9.2, and 17.8/13.6 months, respectively), translating to 2.3, 2.3, 0.6, and 0.9 discounted QALYs. CONCLUSION: Alternative methods produced consistent results, showing T-DXd is associated with substantial gains in OS and QALYs versus eribulin, and capecitabine. Modelled median OS results were similar to a later data-cut (median of 29.1 months, March 2021 data-cut). The modelling approach in which an HR was applied to the T-DM1 OS curve informed a submission to the National Institute for Health and Care Excellence.

Cost Effectiveness of Inclisiran in Atherosclerotic Cardiovascular Patients with Elevated Low-Density Lipoprotein Cholesterol Despite Statin Use: A Threshold Analysis.

BACKGROUND: Inclisiran is a novel, cholesterol-lowering therapy, with a long duration of effect, administered every 6 months (subcutaneously by a healthcare professional). In the ORION-10 trial in US patients with atherosclerotic cardiovascular disease (ASCVD) in addition to maximum tolerated statins, with or without ezetimibe, inclisiran demonstrated statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) of up to 51%. This is the first peer-reviewed publication to investigate the price at which inclisiran is cost effective in the US. OBJECTIVE: The aim of this study was to determine the maximum price at which inclisiran is cost effective in addition to standard of care, in US patients with ASCVD, versus standard of care alone, at different willingness-to-pay thresholds. DESIGN, SETTING AND PARTICIPANTS: A lifetime Markov model from the US health system perspective, including 15 health states, was used to evaluate the cost effectiveness of inclisiran. The following states were separated by time from a previous cardiovascular event (0-1 years, 1-2 years, 2+ years ['stable']): initial, unstable angina, myocardial infarction, and stroke. Additional states included revascularization and death (cardiovascular or non-cardiovascular causes). Baseline risk of cardivoascular events were from US database sources or published literature. Reductions in LDL-C from inclisiran were from the ORION-10 trial. LDL-C reduction was used to adjust baseline risk of cardiovascular events, based on established relationships between 1 mmol/L reduction in LDL-C and decreases in cardiovascular events, from the Cholesterol Treatment Trialists studies. The population included adults with a history of ASCVD, and LDL-C ≥ 70 mg/dL, despite maximum tolerated doses of statin therapy. INTERVENTIONS: Inclisiran as an adjunct to standard of care, compared with standard of care alone. MAIN OUTCOMES AND MEASURES: The threshold price of inclisiran. RESULTS: Inclisiran as an adjunct to standard of care resulted in threshold annual inclisiran prices of $6383, $9973, and $13,563 at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per quality-adjusted life-year, respectively. Probabilistic sensitivity analysis showed that at a threshold of $100,000 per QALY, inclisiran had a 100% probability of being cost effective, with an annual price below $9000. At the publicly available price of $3250 per dose, inclisiran was found to have an incremental cost-effectiveness ratio just above the $50,000 per QALY threshold, of $51,686. CONCLUSIONS AND RELEVANCE: This study identified the price at which inclisiran is cost effective for the US health system, at generally accepted willingness-to-pay thresholds.