AN ECONOMIC EVALUATION OF ALTERNATIVE TESTTREAT STRATEGIES TO DIRECT HER2 TARGETED BREAST CANCER TREATMENT BASED ON CANADIAN PRACTICE PATTERNS

Abstract

Background and Objectives: Economic evaluation and decision analysis provide a framework to evaluate incremental costs and effects associated with alternative health interventions. These methods can also be used as a tool to evaluate alternative clinical behaviours or practice patterns. The objective of this thesis was to investigate the impact of current Canadian practices in human epidermal growth factor receptor-2 (HER2) testing to target trastuzumab in early-stage breast cancer (BC). Methods: Project 1: A systematic review of previous trastuzumab and HER2 testing economic analyses was conducted to identify methodological gaps and key lessons. Project 2: A population-level, retrospective cohort was studied to determine HER2 testing and trastuzumab treatment patterns in Ontario early-stage BC patients. Project 3: A cost-utility analysis of alternative test-treat strategies was conducted using a Markov model of BC calibrated to the Canadian setting, and incorporating Project 2 findings.

Results: Project 1: Previous economic evaluations demonstrated that HER2 test accuracy and sequencing were key considerations when modelling the cost-effectiveness of trastuzumab treatment. Consideration of local testing and treatment practices was lacking. Project 2: HER2 testing and treatment practice differed from guidelines, where documentation was available. Only 88% of equivocal results were confirmed, while 57% of HER2 positive patients received trastuzumab. Project 3: Calibration of the BC model minimised gaps between trial-based survival and expected Canadian survival patterns. Deviations from guidelines in practice suggest that primary testing with fluorescence in situ hybridization (FISH) would produce greater health gains at a reduced cost vs. primary immunohistochemistry with FISH confirmation. This finding was more apparent as the prevalence of HER2 positive disease increased. Introduction of newer in situ hybridisation tests may be cost-effective as well. Conclusions: Practice deviations from guidelines are an important consideration when modelling the cost-effectiveness of trastuzumab therapy. Underlying local disease progression and prevalence can also significantly impact outcomes.