Collaboration led to practice-changing results in the HERceptin® Adjuvant trial
The founding project for Frontier Science Scotland (FSS), which we started work on in 2002, has turned out to be one of our most significant to date. The HERA trial delivered outstanding results and has influenced changes in the standard of care for those with HER2-positive breast cancer. Our collaboration with numerous study partners has since led to other important projects for Frontier Science Scotland, including the ALTTO and APHINITY trials.
HERA was a randomised three-arm adjuvant trial comparing observation versus one and two years of Herceptin® in women with early stage HER2-positive breast cancer. Herceptin® is a brand name for trastuzumab, a recombinant monoclonal antibody against the HER2 receptor. It was administered to women with HER2-positive primary breast cancer who had already had systemic treatment, including surgery, chemotherapy, and radiotherapy, where appropriate.
This was a multi-centre trial involving 5102 patients enrolled from hospitals in 39 countries between December 2001 and June 2005. The primary end-point was disease-free survival, with overall survival and cardiac safety as secondary endpoints.
Our collaborators on HERA
We collaborated with the Breast International Group (BIG) and the coordinating group, Institut Jules Bordet (IJB) – formerly known as BrEAST – on many aspects of trial management for HERA. We also worked closely with our affiliate, the Frontier Science Foundation in the USA, on the statistical analyses. The Swiss multinational healthcare company, Roche, sponsored this clinical trial.
Our areas of responsibility
We were employed as data managers, as the Independent Statistical Centre to carry out statistical analysis, and were also responsible for cardiac data monitoring and Independent Data Monitoring Committee administration. Key FSS staff were on the trial governing committees.
Only data managers from IJB and our statisticians had full access to the database. Marion Procter, now Senior Statistician at FSS and a key member of the HERA study team, was involved in running the interim analysis in 2005 at one-year median follow-up which led to registration of trastuzumab, and in subsequent efficacy analysis. FSS remained involved until the completion of the follow-up on patients in 2015. We have also worked on numerous associated research projects.
Where the results were published
The first results of the study were published in the New England Journal of Medicine in October 2005. The results of two years of Herceptin versus one year of Herceptin were published in The Lancet in July 2013. Manuscripts on cardiac safety and from several research projects have been published. The final efficacy results were published in The Lancet in 2017.
Key study outcomes
The HERA results were practice-changing, and according to the manufacturer, Herceptin® has now been used to treat over 2.3 million patients.
Keep an eye out for our upcoming case studies which delve into our involvement in the HERA clinical trial. You can also discover more about the work of our senior statistician, Marion Procter, in our next blog.
A pooled analysis of the cardiac events in the trastuzumab adjuvant trials
An article published in The Lancet shares the results from the final analysis of the HERceptin Adjuvant (HERA) trial.
Trastuzumab-associated cardiac events at 8 years of median follow-up in the HERceptin Adjuvant Trial (HERA)
Disease-Free Survival According to Degree of HER2 Amplification for Patients Treated With Adjuvant Chemotherapy With or Without 1 Year of Trastuzumab: The HERA Trial
HERA Research | Annals of Oncology | Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial
An assessment of the magnitude of the clinical benefit of trastuzumab for subpopulations using data from the Herceptin Adjuvant (HERA) study.
Results of the first planned interim analysis of HERA showed significant improvements in disease-free survival among women with HER2-positive breast cancer.