Cost-effectiveness analysis of trastuzumab for early breast cancer in Brazil.

BACKGROUND: Adjuvant chemotherapy with trastuzumab for HER2 positive breast cancers has brought considerable benefits to disease-free survival and overall survival. OBJECTIVE: To conduct a cost-effectiveness analysis of the treatment of patients with early and locally advanced HER2 positive breast cancer, within the scope of the Brazilian public health system, comparing adjuvant chemotherapy with and without trastuzumab, for 1 year of treatment. METHODS: A 4-state Markov model was developed to estimate strategy costs and outcomes. RESULTS: Based on the proposed model, we verified an incremental benefit of trastuzumab therapy compared to treatment without trastuzumab with 0.84 quality-adjusted life years (QALY) and 1.16 life years gained (LYG). The use of adjuvant chemotherapy with trastuzumab has an ICER of US$19,599.26 for each quality-adjusted life year and US$14,180.68 for each life year gained in relation to chemotherapy without trastuzumab. CONCLUSION: In Brazil, adjuvant chemotherapy with trastuzumab may be considered cost-effective only if a cost-effectiveness threshold is stipulated with the value starting at three times the Brazilian GDP per capita for QALY or two times the Brazilian GDP per capita for LYG, from health system perspective.

Cost-effectiveness Analysis of Ado-trastuzumab Emtansine (T-DM1) for the Adjuvant Treatment of Patients With Residual Invasive HER2+ Early Breast Cancer in the United States.

OBJECTIVE: Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States. MATERIALS AND METHODS: A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature. RESULTS: T-DM1 dominated trastuzumab, yielding lower lifetime costs (-$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results. CONCLUSION: Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes.

Direct Medical Costs of Advanced Breast Cancer Treatment: A Real-World Study in the Southeast of The Netherlands.

OBJECTIVES: Policy makers increasingly seek to complement data from clinical trials with information from routine care. This study aims to provide a detailed account of the hospital resource use and associated costs of patients with advanced breast cancer in The Netherlands. METHODS: Data from 597 patients with advanced breast cancer, diagnosed between 2010 and 2014, were retrieved from the Southeast Netherlands Advanced Breast Cancer Registry. Database lock for this study was in October 2017. We report the observed hospital costs for different resource categories and the lifetime costs per patient, adjusted for censoring using Lin's method. The relationship between patients' characteristics and costs was studied using multivariable regression. RESULTS: The average (SE) lifetime hospital costs of patients with advanced breast cancer were €52 709 (405). Costs differed considerably between patient subgroups, ranging from €29 803 for patients with a triple-negative subtype to €92 272 for patients with hormone receptor positive and human epidermal growth factor receptor 2 positive cancer. Apart from the cancer subtype, several other factors, including age and survival time, were independently associated with patient lifetime costs. Overall, a large share of costs was attributed to systemic therapies (56%), predominantly to a few expensive agents, such as trastuzumab (15%), everolimus (10%), and bevacizumab (9%), as well as to inpatient hospital days (20%). CONCLUSIONS: This real-world study shows the high degree of variability in hospital resource use and associated costs in advanced breast cancer care. The presented resource use and costs data provide researchers and policy makers with key figures for economic evaluations and budget impact analyses.

Intravenous and subcutaneous formulations of trastuzumab, and trastuzumab biosimilars: implications for clinical practice.

Trastuzumab is a biologic therapy indicated for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer and metastatic gastric cancer. Trastuzumab was originally approved as an intravenous (IV) formulation but has since been developed for subcutaneous (SC) administration for patients with HER2-positive breast cancer. Both formulations demonstrate generally comparable pharmacological and clinical profiles. Therefore, when deciding between treatment options, factors such as the route of administration, patient preference, value and cost must be considered. Studies comparing IV with SC trastuzumab indicate that each formulation offers unique advantages to patients depending on their individual needs. Concurrent with the development of SC trastuzumab, IV trastuzumab biosimilars comprise another treatment option that, in view of their reduced cost, might improve patient access and increase cost-effectiveness for healthcare providers and payers. In this review, we seek to raise awareness of the current options available for trastuzumab so that healthcare providers can optimally treat patients according to their individual situations and preferences.

Trastuzumab with carboplatin/paclitaxel for treatment of advanced stage and recurrent uterine papillary serous carcinoma: A cost-effectiveness analysis.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is a variant of endometrial cancer that is aggressive and associated with poor outcomes. We sought to evaluate the cost effectiveness of carboplatin/paclitaxel alone versus carboplatin/paclitaxel with trastuzumab among patients with Her2/neu-positive advanced or recurrent UPSC. METHODS: We designed a Markov model in TreeAge Pro 2019 software to simulate management of a theoretical cohort of 4000 patients with Her2/neu-positive advanced or recurrent uterine papillary serous carcinoma (UPSC) followed for four years. In the carboplatin/paclitaxel with trastuzumab strategy, we included the cost of testing for Her2/neu status. We obtained all model inputs from the literature and a societal perspective was assumed. Outcomes included progression-free survival, progression, UPSC-specific mortality, cost, and quality-adjusted life years (QALYs). The intervention was considered cost effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were used to determine the robustness of the results. RESULTS: In our theoretical cohort of 4000 women, treatment with the addition of trastuzumab resulted in 637 fewer deaths and 627 fewer cases of progression compared with treatment with carboplatin/paclitaxel alone. Treatment with trastuzumab was associated with an additional cost of $144,335,895, but was associated with an increase of 2065 QALYs. The ICER was $69,903 per QALY, which was below our willingness-to-pay threshold. Sensitivity analysis demonstrated that this treatment strategy was cost-effective until the cost of 6 months of treatment surpassed $38,505 (baseline input: $27,562). CONCLUSION: We found that the addition of trastuzumab to carboplatin/paclitaxel was a cost-effective treatment strategy for patients with advanced/recurrent Her2/neu-positive UPSC.

Economic evaluation of adjuvant trastuzumab therapy for HER2-positive early-stage breast cancer: systematic review and quality assessment.

INTRODUCTION: As the availability of new economic evaluations (EE) on adjuvant trastuzumab therapy for early-stage breast cancer (EBC) with HER2-positive since last search and other EEs missed warrant a more extensive review, this study aimed to systematically review EEs of adjuvant trastuzumab compared with chemotherapy alone for HER2-positive EBC. AREA COVERED: The search was performed in February 2019 using MEDLINE and Scopus. Reviewers independently selected studies based on eligibility criteria, extracted data, assessed quality of reporting, and appraised quality of data sources. EXPERT OPINION: 22 studies were included which were from high-income (HICs) and upper-middle income countries (UMICs). Incremental cost-effectiveness ratios (ICERs) from HICs were within their cost-effectiveness thresholds and ranged from 6,018 to 78,929 USD per quality-adjusted life year (QALY) gained. ICERs from UMICs mostly exceeded their thresholds ranging from 3,526 to 174,901 USD per QALY gained. Evidence shows cost-effectiveness of trastuzumab for HER2-positive EBC in HICs. There were no methodological variations. The extent and adequacy of reporting were high. The quality of data sources was moderate to high. The quality of future EEs can be improved by enhancing the reporting quality, by using context-based data and real-world efficacy data, which would impact cost-effectiveness.

Cost-effectiveness analyses of breast cancer medications use in developing countries: a systematic review.

BACKGROUND: Pharmacoeconomic evaluation is important for breast-cancer medications due to their high costs. To our knowledge, no systematic literature reviews of pharmacoeconomic studies for breast-cancer medication use are present in developing-countries. OBJECTIVES: To systematically review the existing cost-effectiveness evaluations of breast-cancer medication in developing-countries. METHODOLOGY: A systematic literature search was performed in PubMed, EMBASE, SCOPUS, and EconLit. Two researchers determined the final articles, extracted data, and evaluated their quality using the Quality of Health-Economic Studies (QHES) tool. The interclass-correlation-coefficient (ICC) was calculated to assess interrater-reliability. Data were summarized descriptively. RESULTS: Fourteen pharmacoeconomic studies published from 2009 to 2019 were included. Thirteen used patient-life-years as their effectiveness unit, of which 10 used quality-adjusted life-years. Most of the evaluations focused on trastuzumab as a single agent or on regimens containing trastuzumab (n = 10). The conclusion of cost-effectiveness analysis varied among the studies. All the studies were of high quality (QHES score >75). Interrater reliability between the two reviewers was high (ICC = 0.76). CONCLUSION: In many studies included in the review, the use of breast-cancer drugs in developing countries was not cost-effective. Yet, more pharmacoeconomic evaluations for the use of recently approved agents in different disease stages are needed in developing countries.

The challenge of sustainability in healthcare systems: economic and organizational impact of subcutaneous formulations for rituximab and trastuzumab in onco-hematology.

Background: This study estimated the economic and organisational impact of using subcutaneous injection (SC) formulations of two monoclonal antibodies (rituximab and trastuzumab) in patients with non-Hodgkin's lymphoma (NHL) and HER2 + breast cancer (BC).Methods: The database of the Unit of Oncology and Haematology of the IRST of Meldola was used. The analysis was structured as follows: i) measurement of the volume of Day-Hospital activity; ii) identification of activities and time to complete the administration; iii) estimate the mean cost of an SC or IV (intravenous infusion); iv) estimate the impact of SC formulations on the volumes of activities provided; v) estimate the social impact of SC or IV formulations.Results: The use of an SC formulation was associated a significant reduction in the time that the patient takes to complete the administration (trastuzumab -1 hr 18 min; rituximab -2 hr 24 min) and in consumption of healthcare resources and related costs for trastuzumab (IV: € 1781; SC: € 1701) and rituximab (IV: € 2116; SC: € 1941).Conclusion: The adoption of the SC formulation for rituximab and trastuzumab can generate a greater value for both the national healthcare system and the patient compared to an IV formulation.

Budget impact analysis of subcutaneous trastuzumab compared to intravenous trastuzumab in Saudi HER2-positive breast cancer patients.

Background: This study was aimed to assess the budget impact of SC trastuzumab compared to IV trastuzumab in patients with HER2-positive breast cancer (BC) from the perspective of the governmental health sector in Saudi Arabia, over a 3-year time horizon.Methods: A model was developed to calculate the direct medical and indirect costs for 394 incidents HER2-positive BC patients per year who would receive SC trastuzumab compared to IV formulation. We calculated drug acquisition costs for fixed, loading, and subsequent doses of trastuzumab. One-way sensitivity analysis was conducted.Results: Two scenarios were modeled: the first scenario evaluated the impact of gradual replacement of IV formulation by SC, the second scenario, evaluated impact of totally replacing IV formulation. The total annual costs in the first scenario were estimated to be SAR 177 million (USD 98 million) for IV trastuzumab compared to SAR 143 million (USD 79 million) for SC formulation, leading to a total budget saving of SAR 34,527,346 (USD 19,181,858). In the second scenario, the total annual costs were estimated to be SAR 108 million (USD 60 million) for SC trastuzumab compared to SAR 177 million (USD 98 million) for IV formulation, leading to budget savings of SAR 69,054,692 (USD 36,363,717).Conclusion: Benefits of the SC formulation over IV infusions are being converted to realistic monetary benefits for all providers and payers.

Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)-Positive Breast Cancer.

Importance: The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed. Objective: To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer. Design, Setting, and Participants: In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020. Exposure: There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1. Main Outcomes and Measures: Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative. Results: In the base-case analysis, costs ranged from $415 833 (strategy 3) to $518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/QALY) and was associated with the highest net benefit. Conclusions and Relevance: These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered.

Adjuvant trastuzumab in early HER2-positive breast cancer: Journeying towards the optimal duration of therapy in South Africa.

Trastuzumab was added to the South African Essential Medicines List (EML) in 2017 for the adjuvant management of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. However, access has remained inconsistent, as some provinces continue to regard trastuzumab as unaffordable within the contexts of their respective oncology budgets. The intention of providing access to trastuzumab through its inclusion on the EML, therefore, has not been met. The National EML Committee (NEMLC) recently reviewed newly published peer-reviewed information investigating the impact of a shorter trastuzumab treatment period on both clinical efficacy and safety. On account of this review, and with a view to improving access while reducing cost and toxicity, the NEMLC has revised the duration of trastuzumab therapy, i.e. from 12 months to 6 months in the adjuvant management of early HER2-positive breast cancer. This article explores and reports on the data used to make this policy amendment.

Real-World Setting Cost-Effectiveness Analysis Comparing Three Therapeutic Schemes of One-Year Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer from the Cyprus NHS Payer Perspective.

INTRODUCTION: This study is one of the first real-world cost-effectiveness analyses of one-year adjuvant trastuzumab used in HER2-positive early female breast cancer in comparison to chemotherapy alone. It is just the second one in Europe, the first one in Cyprus, and the fourth one worldwide ever carried out using real-world data. METHODS: Using a Markov model (four health states), a cost-effectiveness analysis was carried out both over 20 years and for a lifetime horizon. The sampling method used in this study was the randomized sampling of 900 women. RESULTS: The findings for the 20-year horizon showed that all trastuzumab arms were more cost-effective, with a willingness-to-pay threshold of only €60,000 per quality-adjusted life year (QALY) [incremental cost-effectiveness ratios (ICER): €40,436.10/QALY]. For the lifetime horizon, with thresholds of €20,000, €40,000, and €60,000/QALY, all trastuzumab arms were found to be more cost-effective (ICER: €17,753.85/QALY). Moreover, for the 20-year and the lifetime horizons, with thresholds of €20,000/QALY, €40,000/QALY, and €60,000/QALY, the most cost-effective of the three subgroups (anthracyclines and then trastuzumab, no anthracyclines and then trastuzumab, and anthracyclines, taxanes, and trastuzumab) was that of anthracyclines and then trastuzumab (ICER: €18,301.55/QALY and €8954.97/QALY, respectively). CONCLUSIONS: The study revealed that adjuvant trastuzumab for one year in female HER2-positive early breast cancer can be considered cost-effective.

Hospital-based or home-based administration of oncology drugs? A micro-costing study comparing healthcare and societal costs of hospital-based and home-based subcutaneous administration of trastuzumab.

OBJECTIVE: To investigate resource use and time investments of healthcare professionals, patients and their family and to compare healthcare and societal costs of one single hospital-based and one single home-based subcutaneous administration of trastuzumab in The Netherlands. METHOD: We conducted a bottom-up micro-costing study. Patients diagnosed with HER2+ early or metastatic breast cancer were recruited in four Dutch hospitals. For healthcare costs, data were collected on drug use, consumables, use of healthcare facilities, time of healthcare professionals, and travelling distance of the nurse. For societal costs, data were collected on patient and family costs (including travelling expenses and time of informal caregivers) and productivity losses of paid and unpaid work. RESULTS: Societal costs of one single administration of SC trastuzumab were €1753 within the home-based and €1724 within the hospital-based setting. Drug costs of trastuzumab were identical in both settings (€1651). Healthcare costs were higher for home-based administration (€91 versus €47) mainly because of more time of healthcare professionals (110 versus 38 minutes). Costs for patient and family were, however, lower for home-based administration due to travelling expenses (€7 versus €0) and time of informal caregivers (€14 versus €4). Costs for productivity losses were similar for both settings. CONCLUSIONS: Home-based subcutaneous administration of trastuzumab is more time consuming for healthcare professionals and therefore more costly than hospital-based administration. The total budget impact can be large considering that a large number of patients receive a large number of cycles of oncology treatments. If home-based administration is the way forward, novel approaches are crucial for ensuring efficiency of home-based care.

Cost-minimization analysis of subcutaneous versus intravenous trastuzumab administration in Chilean patients with HER2-positive early breast cancer.

PURPOSE: Trastuzumab (TZM) improves survival and the risk of recurrence among patients with early-stage HER2+ breast cancer (BC). TZM treatment can be given intravenously (IV-TZM) or subcutaneously (SC-TZM). Although both methods have similar efficacy and safety, they differ in dosage and administration. Previous studies of cost minimization determined that SC-TZM is associated with lower costs than IV-TZM; however, those studies did not include the costs associated with body weight-based dosage and the treatment of adverse drug reactions (ADRs). METHODS/PATIENTS: We performed a model-based cost-minimization analysis. The analysis included direct and indirect medical costs associated with TZM preparation (adjusted by body weight) and administration and also costs due to severe ADRs and non-medical costs that occurred during the total treatment course (18 cycles). We performed a sensitivity analysis to test the robustness of the results across various TZM costs and patient body weights. RESULTS: The overall cost (in USD) of IV-TZM treatment was $83,309.1 per patient compared with $77,067.7 per patient for SC-TZM. Thus, one year of SC-TZM treatment cost $6,241.4 less per patient than one year of IV-TZM treatment. The sensitivity analysis revealed that the results were mainly driven by the price of each TZM vial and body weight. CONCLUSION: SC-TZM is a cost-saving therapy for Chilean patients with early-stage HER2+ BC. Given their similar efficacy and safety, we suggest the use of SC formulations rather than IV formulations. The use of SC-TZM instead of IV-TZM may have a significant economic impact on public/private healthcare systems.

Cost-effectiveness of six months versus 1-year adjuvant trastuzumab in HER2 positive early breast cancer in Egypt.

Introduction: Breast cancer is the most prevalent cancer among women in Egypt. Trastuzumab is administered with chemotherapy for patients with HER2-positive advanced breast cancer (HER2 + ve ABC) in the metastatic and adjuvant settings resulting in improved treatment outcomes, and long-term follow-up. Some studies have evaluated whether equivalent outcomes can be achieved with reduced treatment duration. This study evaluates the cost-effectiveness of 6-month versus 1-year trastuzumab treatments from payer perspective over a 10 year time horizon.Methods: A half-cycle corrected Markov model was developed with five mutually exclusive health states; patient with HER2 +ve ABC, disease-free survival (DFS), local or regional relapse, metastatic relapse, and death. A cycle length of 6 months was applied, direct medical costs including cost of treatments, day-care, surgery, health states and follow-up visits were collected, and indirect costs such as lost productivity were not estimated. The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted.Results: Among the HER2 +ve ABC patient population in Egypt, the total QALYs of the 6-month trastuzumab were estimated to be 2.99 compared with 2.93 for the 1-year trastuzumab which resulted in a difference of 0.06 QALYs. The total costs were EGP 271,647 ($106,947) and EGP 381,248 ($150,097), respectively. These costs yielded an ICER of -109,600 EGP/QALY (-43,149 $/QALY) for the 6-month trastuzumab. The 6-month trastuzumab is a dominant strategy when compared to 1-year trastuzumab, resulting in improved effectiveness at a reduced cost. All analyses results confirmed the dominance of 6-month trastuzumab and our model robustness.Conclusions: This study concluded that 6-month trastuzumab is a cost-effective option when compared to 1-year trastuzumab in patients with HER2 +ve ABC in Egypt. Our findings provide health care decision makers with additional insights to best allocate available resources concurrently with the improvement of the Egyptian patient's outcomes.

A cost-effectiveness analysis of trastuzumab-containing treatment sequences for HER-2 positive metastatic breast cancer patients in Taiwan.

OBJECTIVE: Treatment options for HER-2-positive metastatic breast cancer (mBC) patients have expanded markedly since trastuzumab approval in 1998. Several other regimens are now available, including pertuzumab plus trastuzumab plus docetaxel, T-DM1, capecitabine plus lapatinib, and trastuzumab plus lapatinib. This study assesses the cost-effectiveness of four treatment sequences for HER-2-positive mBC according to the Taiwanese National Health Insurance Administration (TNHIA). METHODS: Costs (U.S. Dollars) and effectiveness (quality-adjusted life years) of four treatment sequences for HER-2-positive mBC patients were examined using a Markov model over a lifetime horizon. Transition probabilities, disease progression, and probability of adverse events and survival were derived from clinical trial data. Costs and health utilities were estimated from TNHIA, Taipei Medical University Hospital, and the literature. Deterministic, probabilistic sensitivity analyses and a scenario analysis examined parameter uncertainty and accounted for drug wastage in dosage and cost calculations. RESULTS: Sequence 3 (1st line: trastuzumab plus docetaxel; 2nd line: T-DM1; 3rd line: trastuzumab plus lapatinib) was the most cost-effective sequence followed by sequence 1 (1st line: pertuzumab plus trastuzumab plus docetaxel; 2nd line: T-DM1; 3rd line: capecitabine plus lapatinib), and sequence 4 (1st line: trastuzumab plus docetaxel; 2nd line: trastuzumab plus lapatinib; 3rd line: trastuzumab plus capecitabine), respectively. The model was sensitive to costs and transition probabilities, but not particularly sensitive to the wastage assumption. CONCLUSIONS: From the perspective of the TNHIA, trastuzumab plus docetaxel as 1st line followed by T-DM1 and trastuzumab plus lapatinib as 2nd and 3rd line represents the most cost-effective strategy among the four sequences considered for treating HER-2-positive mBC patients.

Cost-utility analysis of adjuvant trastuzumab therapy for HER2-positive early-stage breast cancer in the Philippines.

BACKGROUND: Breast cancer is the leading malignancy among Filipino women, with about 23.50% of cases characterized by human epidermal growth factor receptor-2 (HER2) overexpression. Trastuzumab, in addition to standard chemotherapy, is currently recommended as primary treatment for HER2-positive early-stage breast cancer (EBC) in the adjuvant settings, and has been listed in the Philippine National Formulary (PNF) since 2008, but with no current evidence yet on its value for money, to date. Hence, despite several policy enablers, its accessibility remains to be limited in the Philippines. We performed an economic evaluation to assess the cost-effectiveness and budget impact of adjuvant trastuzumab therapy for HER2-positive EBC in the Philippines, using healthcare system and societal perspectives, in aid of guiding coverage decisions. METHODS: A Markov model-based cost-utility and budget impact analyses were conducted to estimate the total costs incurred and outcomes gained in using 1 year of adjuvant trastuzumab added to standard chemotherapy versus standard chemotherapy alone, over a lifetime horizon. We discounted both costs and outcomes at 3.5% per annum. Parameters were estimated using country survival data, systematic review and meta-analysis of the relative treatment effect, local and international cost data, and published utility data. Univariate and probabilistic sensitivity analyses were used to account for parameter uncertainty. RESULTS: Trastuzumab therapy was dominated with an incremental cost-effectiveness ratio (ICER) at PHP 453,505 per QALY gained from a healthcare system perspective or PHP 458,686 per QALY gained from a societal perspective, with 10% cost-effectiveness probability at the country cost-effectiveness threshold of PHP 120,000 per QALY gained. National implementation will cost an additional amount of PHP 13,909 million in year one alone, plus about PHP 2000 to 3000 million annually for the succeeding fiscal years. CONCLUSION: At its current cost, 1 year of adjuvant trastuzumab therapy compared to standard chemotherapy alone for HER2-positive EBC does not represent value for money in the Philippines. Its current cost will have to significantly lower down by one-half to achieve cost-effectiveness.

Cost-Effectiveness Analysis of Adjuvant Neratinib Following Trastuzumab in Early-Stage HER2-Positive Breast Cancer.

BACKGROUND: Disease-free survival (DFS) in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer is significantly greater with the addition of neratinib after adjuvant trastuzumab versus no additional therapy. However, it remains uncertain whether these survival gains represent good value for the money, given the substantial cost of neratinib. OBJECTIVE: To evaluate clinical and economic implications of adding neratinib after adjuvant trastuzumab based on results from the phase III ExteNET trial. METHODS: A 3-state Markov model was developed to estimate the cost-effectiveness of neratinib for women with early-stage (I-III) HER2-positive breast cancer. Five-year recurrence rates were derived from the ExteNET trial. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical expenditures. The analysis was performed from a payer perspective over a lifetime horizon. One-way sensitivity and probabilistic analyses were conducted to evaluate uncertainty. RESULTS: Total cost of neratinib following adjuvant trastuzumab was $317,619 versus $152,812 for adjuvant trastuzumab alone. A gain of 0.4 QALYs (15.7 vs. 15.3) and 0.1 years of projected life expectancy (18.3 vs. 18.2) favored neratinib after trastuzumab versus trastuzumab alone. The neratinib cost per QALY gained was $416,106. At standard willingness-to-pay thresholds of $50,000, $100,000, and $200,000 per QALY gained, neratinib has a probability of 2.8%, 16.7%, and 33.9% of cost-effectiveness, respectively. The cost per QALY gained in a scenario analysis only including patients with hormone-receptor positive disease was $275,311. CONCLUSIONS: Based on 5-year data from ExteNET, neratinib following adjuvant trastuzumab is not projected to be cost-effective, even among those patients shown to derive the greatest clinical benefit. Future analyses should reassess the cost-effectiveness associated with neratinib treatment as trial data mature. DISCLOSURES: No outside funding supported this study. Roth reports consulting fees from Genentech. Steuten reports grants from AstraZeneca, EMD Serono, and Genomic Health, along with personal fees from Agendia, unrelated to this study. The other authors have no conflicts of interest in connection with this study.

Uncertainty and Coverage With Evidence Development: Does Practice Meet Theory?

OBJECTIVES: In theory, a successful coverage with evidence development (CED) scheme is one that addresses the most important uncertainties in a given assessment. We investigated the following: (1) which uncertainties were present during the initial assessment of 3 Dutch CED cases, (2) how these uncertainties were integrated in the initial assessments, (3) whether CED research plans included the identified uncertainties, and (4) issues with managing uncertainty in CED research and ways forward from these issues. METHODS: Three CED initial assessment dossiers were analyzed and 16 stakeholders were interviewed. Uncertainties were identified in interviews and dossiers and were categorized in different causes: unavailability, indirectness, and imprecision of evidence. Identified uncertainties could be mentioned, described, and explored. Issues and ways forward to address uncertainty in CED schemes were discussed during the interviews. RESULTS: Forty-two uncertainties were identified. Thirteen (31%) were caused by unavailability, 17 (40%) by indirectness, and 12 (29%) by imprecision. Thirty-four uncertainties (81%) were only mentioned, 19 (45%) were described, and the impact of 3 (7%) uncertainties on the results was explored in the assessment dossiers. Seventeen uncertainties (40%) were included in the CED research plans. According to stakeholders, research did not address the identified uncertainty, but CED research should be designed to focus on these. CONCLUSIONS: In practice, uncertainties were neither systematically nor completely identified in the analyzed CED schemes. A framework would help to systematically identify uncertainty, and this process should involve all stakeholders. Value of information analysis, and the uncertainties that are not included in this analysis should inform CED research design.

The Economic Impact of Biosimilars in Oncology and Hematology: The Case of Trastuzumab and Rituximab.

BACKGROUND/AIM: Biosimilar agents are biologic products that have no clinically meaningful differences in terms of quality, efficacy, safety and immunogenicity compared to an already approved reference biological product, with the potential to reduce the costs of biologics. Considering the increasing numbers of oncology biosimilars, it is important to calculate the economic impact of biosimilars in oncology and hemathology, considering trastuzumab and rituximab as examples, with their greatest budgetary impact in Oncology and Hematology Units, respectively. The present analysis was conducted to assess the pharmacological costs of trastuzumab and rituximab originator versus the corresponding approved biosimilars. MATERIALS AND METHODS: Pivotal phase III randomized controlled trials (RCTs) were considered for the approved indications in neoadiuvant breast cancer (BC) and in first-line treatment for advanced follicular lymphoma. Pharmacological costs necessary to get the benefit in the cancer outcomes: i) time to treatment failure (TTF) and ii) pathological complete response (pCR) in biosimilars and originators were calculated. The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). RESULTS: Our analysis evaluated 5 phase III RCTs, including 2,362 patients. The economic advantage of biosimilars versus (vs.) originator is 274 € (rituximab) and from 3,283 € to 6,310 € (trastuzumab) per month for TTF (about 40% less than the originator). CONCLUSION: Combining pharmacological costs of drugs with the measure of efficacy represented by TTF and pCR, biosimilars of rituximab and trastuzumab are cost-effective treatments for advanced follicular lymphoma and breast cancer.