Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: protocol detailing observations in a whole of population cohort

Abstract

BackgroundThe management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia.Methods/designOur ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research.Ethics and disseminationEthics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments.

Adherence to prescribing restrictions for HER2-positive metastatic breast cancer in Australia: a national population-based observational study (2001-2016)

“…The Australian healthcare setting and the datasets used in this study have been described in our research protocol. [6] Briefly, Australia maintains a publicly funded, universal healthcare system entitling all citizens and permanent residents to subsidised medicines through the Pharmaceutical Benefits Scheme (PBS). The Herceptin Program, a separate funding program sitting outside of the PBS, provided subsidised access to trastuzumab for HER2+MBC from statistics@humanservices.gov.au) regarding access to the source data and data custodian approval.…”

“…From July 2015, pertuzumab was funded for use as first-line therapy in combination with trastuzumab and a taxane; and T-DM1 was funded as monotherapy after treatment with pertuzumab. [6] Based on these restrictions, we defined the following treatment as non-adherent:…”

“…[20] Ethics and data access approvals Our study was approved by the NSW Population and Health Services Research Ethics Committee (Approval Number: 2010/02/213) and data access was granted by the Australian Department of Human Services (DHS) External Request Evaluation Committee (Approval Numbers: MI1474, MI1475, MI1477, MI5858). Individual consent for the release of these data has been waived according to the Australian Privacy Act of 1988 [6]. Direct access to the data and analytical files to other individuals or authorities is not permitted without the express permission of the approving human research ethics committees and data custodians.…”

“…In Australia, HER2-targeted therapies are publicly-subsidised for HER2+MBC with specific restrictions governing their use. [6] These restrictions are based on evidence from the pivotal clinical trials of these medicines, [2-4, 7, 8] and are designed to ensure that the medicines are used in ways deemed cost-effective. Our own research suggests that between 2001 and 2015 there was substantial heterogeneity in the use of trastuzumab for HER2+MBC in terms of duration of therapy and chemotherapeutic partners, leading us to believe prescribing restrictions were often not adhered to.…”

A Critical Review of Economic Evaluations of Trastuzumab in the Treatment of Early Stage HER2 Positive Breast Cancer

“…Targeted therapy has proved to be pivotal in the management of HER2 positive breast cancer. In comparison with cytotoxic chemotherapy alone, the addition of HER2-targeted therapies markedly improves response rates, survival outcomes (in terms of Disease-Free Survival (DFS)/Progression-Free Survival (PFS) and Overall Survival (OS)) in patients with HER2-positive breast cancer treated in the neoadjuvant (treatment given to shrink the tumor before the main treatment), adjuvant (treatment given to help the main treatment) or metastatic (when the cancer has spread beyond the breast to other organs) settings [34]. Trastuzumab (Herceptin, Genetech), recombinant humanized monoclonal antibody, was the first medication in this group.…”