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OBJECTIVES: Trastuzumab deruxtecan (T-DXd) was recently recommended by the Committee for Medicinal Products for Human Use as a treatment for adult patients with unresectable or metastatic HER2-positive breast cancer, who had received a prior anti-HER2-based regimen. In our study, we evaluated the cost-effectiveness of T-DXd compared with ado-trastuzumab emtansine (T-DM1) for this indication in Finland. METHODS: A three-state partitioned survival analysis model was developed with a payer's perspective. Time to event data from the DESTINY-Breast03 (DB-03) trial were extrapolated over a lifetime horizon either directly-for progression-free survival and time to treatment discontinuation-or using an alternative approach utilizing long-term T-DM1 survival data and DB-03 data-for overall survival. Discount rates of 3% were applied for costs and effects. Inputs were sourced from the Medicinal Products Database from Kela, Helsinki University Hospital service price list, Finnish Medicines Agency assessments, clinical experts, and DB-03. Sensitivity analyses were performed to characterize and demonstrate parameter uncertainties in the model. RESULTS: Total quality-adjusted life years (QALYs) and life years (LYs) gained for T-DXd compared with T-DM1 were 1.93 and 2.56, respectively. Incremental costs for T-DXd compared with T-DM1 were 106,800, resulting in an ICER of 55,360 per QALY gained and an ICER of 41,775 per LY gained. One-way sensitivity analysis showed the hazard ratio of T-DXd vs T-DM1 for OS was the most influential parameter. The probabilistic sensitivity analysis showed similar results to the base case. CONCLUSIONS: T-DXd is cost-effective based on surrogate WTP thresholds of 72,000 and 139,000 per QALY.
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INTRODUCTION: The selective estrogen receptor degrader fulvestrant is approved for the first-line treatment of postmenopausal patients with hormone receptor-positive (HR+), locally advanced or metastatic breast cancer who have not received prior endocrine therapy. We evaluated the cost-effectiveness of fulvestrant versus comparator treatments in endocrine therapy-naïve patients with locally advanced or metastatic breast cancer. METHODS: A three-health-state (progression free, progressed disease, and death) partitioned survival model from the UK National Health Service and Personal Social Services perspective was developed to extrapolate study data for the cumulative probability of progression-free survival and overall survival to a lifetime (30-year) horizon. Relative comparator data were derived from a systematic literature review-informed network meta-analysis. Sensitivity analyses were applied to assess the impact of uncertainty in the parameter input values on the results. RESULTS: Over a lifetime horizon (30 years), the incremental cost (British pounds sterling) per patient associated with fulvestrant treatment was £18,867 versus anastrozole, £23,097 versus letrozole, and £17,131 versus tamoxifen, with incremental quality-adjusted life-years of 0.55, 0.77, and 0.76, respectively, and incremental cost-effectiveness ratios of £34,109, £29,827, and £22,532, respectively. The largest difference in costs between fulvestrant and the comparators was related to treatment costs. CONCLUSIONS: Results suggest that fulvestrant could potentially be a cost-effective option compared with other endocrine monotherapies (anastrozole, letrozole, and tamoxifen) for treating endocrine therapy-naïve, postmenopausal women with HR+, locally advanced or metastatic breast cancer.
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OBJECTIVES: In Sweden, breast cancer (BC) represents 30% of newly diagnosed cancers and is the most common cancer in women. For hormone-dependent BC, endocrine therapies varying in efficacy and price are available. The aim of this study is to assess the cost effectiveness of fulvestrant 500 mg as a second-line hormonal therapy for postmenopausal women with estrogen receptor-positive metastatic or locally advanced BC versus letrozole, anastrozole, and exemestane in Sweden. METHODS: A three-state (pre-progression, post-progression, and death) partitioned-survival model was used to estimate progression-free (PFS) and overall survival (OS) by extrapolating trial results beyond the trial period to capture costs and benefits over a lifetime perspective. The comparative effectiveness was sourced from a network meta-analysis. The evaluation was conducted from a Swedish national payer perspective; costs, resource use, and quality of life were based on published sources and expert opinion. RESULTS: Compared to anastrozole, letrozole, and exemestane the incremental cost-effectiveness ratios (ICERs) were 33,808, 33,883, and 49,225 per QALY with incremental costs of 13,283, 14,986, and 13,862, and incremental QALYs of 0.393, 0.442, and 0.282, respectively. Incremental cost per life-year (LY) gained 21,312 (incremental LY of 0.623), 20,338 (incremental LY of 0.737), and 27,854 (incremental LY of 0.498) for respective comparators. Applying the upper and lower credible intervals for PFS/OS from the meta-analysis had the greatest effect on the ICER in the sensitivity analysis. The results were relatively stable when varying other parameters. CONCLUSIONS: Our results indicate that fulvestrant 500 mg may be a cost-effective alternative to aromatase inhibitors at a threshold of 100,000/QALY.
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BACKGROUND: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. OBJECTIVES: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. METHODS: Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. RESULTS: A piecewise model, in which the Kaplan-Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. CONCLUSION: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses.
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BACKGROUND: We conducted a review of randomized trials to compare the overall survival (OS) with fulvestrant 500 mg versus alternative treatment for estrogen receptor-positive advanced breast cancer following endocrine therapy failure. MATERIALS AND METHODS: Hazard ratios (HRs) were obtained by modeling OS data with the Weibull distribution. A fixed-effect Bayesian network meta-analysis was conducted. The evidence network included anastrozole 1 mg, letrozole 2.5 mg, fulvestrant 250 mg, exemestane 25 mg, megestrol acetate 40 mg, and everolimus 10 mg plus exemestane 25 mg as comparators. Post-antiestrogen and post-aromatase inhibitor subgroup networks were analyzed. RESULTS: In the overall analysis, the HRs suggested improved OS for fulvestrant 500 mg versus fulvestrant 250 mg and megestrol acetate 40 mg, and numerically favorable differences with fulvestrant 500 mg versus other comparators. In the antiestrogen subgroup, the HRs suggested improved OS for fulvestrant 500 mg versus fulvestrant 250 mg and megestrol acetate 40 mg; numerical differences in the HRs were seen versus anastrozole 1 mg and letrozole 2.5 mg. In the aromatase inhibitor subgroup, the HRs for OS numerically favored fulvestrant 500 mg versus fulvestrant 250 mg and exemestane 25 mg. CONCLUSION: Acknowledging the limitations of the present network meta-analysis, these findings suggest that fulvestrant 500 mg might provide improved OS versus fulvestrant 250 mg and megestrol acetate 40 mg for treatment of estrogen receptor-positive ABC following endocrine therapy failure. Although OS efficacy versus everolimus 10 mg plus exemestane 25 mg (for overall evidence network), anastrozole 1 mg, exemestane 25 mg, and letrozole 2.5 mg is numerically favorable, additional studies are required to draw formal conclusions.
