Adjuvant Trastuzumab Therapy for Early HER2-Positive Breast Cancer in Iran: A Cost-Effectiveness and Scenario Analysis for an Optimal Treatment Strategy

Abstract

IntroductionClinical guidelines have recommended a 1-year trastuzumab regimen as standard care for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, this recommendation can have a dramatic impact on total drug expenditures in middle-income countries (MICs). We performed a cost-effectiveness analysis from the Iranian healthcare perspective to find an optimum duration of trastuzumab use in Iran.MethodWe compared four treatment strategies comprising chemotherapy and varying durations of trastuzumab use (no trastuzumab, 6, 9 months, and 1 year), and a Markov model and probabilistic sensitivity analysis were used to estimate the costs and effects of the strategies. We then examined the cost effectiveness of the strategies at different willingness-to-pay (WTP) thresholds and ages at onset of treatment.ResultsIncremental costs (versus no trastuzumab) were €8826 (6 months), €13,808 (9 months) and €18,588 (12 months), while incremental quality-adjusted life-years (QALYs) were 0.65 (6 months), 0.87 (9 months) and 1.14 (12 months). At a threshold of 3 × gross domestic product (GDP)/capita (€21,000/QALY) and for patients younger than 59 years, the 6-month protocol was most likely to be cost effective (probability of 42%). At a threshold of 4 × GDP/capita (€28,000/QALY), the 6-month and 1-year regimens were essentially equal in cost effectiveness (37 and 35%, respectively). At this WTP threshold, the 6-month and 1-year regimens were optimal strategies only for patients up to 66 and 44 years of age, respectively.ConclusionIn contrast to clinical guidelines, 6 months of trastuzumab may be the most cost-effective option for Iran. The lower absolute WTP threshold and lower life expectancy compared with high-income countries are two crucial parameters in the cost effectiveness of interventions in MICs. It is therefore necessary to strike a balance between maximum population health and maintaining affordability in these countries.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-017-0557-6) contains supplementary material, which is available to authorized users.

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

“…We identified 22 EEs comparing adjuvant trastuzumab therapy with chemotherapy alone for HER2-positive EBC, published from year 2006 to 2018 (Table 1). As shown in Table 2, studies were mostly from high-income countries (HICs) [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43], while some [44][45][46][47][48][49] were from upper-middleincome countries (UMICs). About half [15,[28][29][30][31][32][33][34][35][36][37]44] were conducted and published as early as 2006 to 2009, which was within the early years of trastuzumab's market entry for HER2-positive early stage indication in 2006.…”

“…More than half [28][29][30][31][32][33][34][35][36][37][38][39][40]44] have been published even before 2013 when the WHO reviewed its inclusion in the WHO Essential Medicines List [50]. In terms of methodology, majority of the studies [30][31][32][36][37][38][39][40][41][42][43][44][45][46][47][48][49] adopted cost-utility analysis, while some [28,29,[33][34][35] used cost-effectiveness analysis. All except two studies [5,10] used decision analytic Markov modeling technique.…”

“…Chemotherapy regimens were varied, but the most common was trastuzumab with anthracycline-taxane combination of standard chemotherapy [28,[30][31][32]38,41,[44][45][46]. More than half of the studies [30,32,33,[37][38][39][40][41][42][43][44][45][46]48] incorporated cardiotoxicity effect of trastuzumab in the analysis. Health care payer or insurance perspective was the most commonly applied [28,[35][36][37][39][40][41]44,45].…”

Do all patients with HER2 positive breast cancer require one year of adjuvant trastuzumab? A systematic review and meta-analysis

“…The drug costs associated with trastuzumab therapy will improve with the introduction of biosimilars, but a shorter duration may still improve patient’s quality of life and decrease the indirect costs associated with treatment such as cardiac monitoring, management of toxicity, and help free up resources for the ever increasing and large current demand for cancer care services. Analyses done have shown favorable cost-benefit for reducing the duration of trastuzumab specific to the region studied and this could have significant implications for improving access to care, especially in resource limited areas [ [47] , [48] , [49] , [50] ]. Additionally, the development of biomarkers to identify lower risk patients who may be ideal candidates for shorter durations of trastuzumab are needed.…”

Six Months vs. 12 Months of Adjuvant Trastuzumab Among Women With HER2-Positive Early-Stage Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

“…Obviously, due to its shorter duration, 6 months of trastuzumab would cost less money compared with 12 months. In addition, a recent study from Iran indicated that 6 months of trastuzumab was a more cost-effective choice than 12 months, with far less incremental spending (8,826 vs. 18,588 pounds) (35). As a result, 6 months of trastuzumab might decrease the financial pressure on thousands of families using trastuzumab, and reduce their psychological burdens in the face of huge medical costs; this shorter duration of trastuzumab is more likely to be affordable for patients in low-and middle-income countries who lack sufficient medical funds.…”