Measuring treatment patterns and outcomes of HER2 positive breast cancer using clinical trials and routine clinical care

In the last two decades the development of targeted cancer therapies has lead to a paradigm shift in the way cancers are being treated. Targeted cancer therapies work differently to traditional cytotoxic chemotherapy by stopping the proliferation and growth of cancer cells by acting on specific molecules in a complex pathway that leads to cancer development. As targeted cancer therapies differ from chemotherapy, it is necessary to rethink the traditional model of drug testing. The aim of this thesis was to describe the way in which the use and outcomes of targeted cancer therapies are measured in clinical trials and in routine clinical care. Whilst this thesis focuses on HER2 breast cancer, although the work detailed in this these has broader applicability across other targeted therapies. Three approaches were used to highlight these issues: a meta analysis of published clinical trials; a routine care study using a clinical audit of prescription data at four cancer centres in NSW, Australia; and a comparison of this prescription data with dispensing claims data in a matched cohort. Whilst ideally studies of routine care are conducted at a whole of population level, this third study helped to assess how well claims data reflects actual practice before undertaking a population level study. This thesis demonstrates the strengths and weaknesses of clinical trials and real world data in measuring targeted cancer therapies to treat HER2 positive breast cancer in both the adjuvant and metastatic setting. Whilst clinical trials remain the gold standard, real world studies can provide a complement to clinical trials in assessing pattern of care. This research will enable a reliable study to be undertaken into adjuvant HER2 patterns of care based on the comparison of prescription and dispensing data undertaken in this thesis