Edinburgh Cancer Informatics and Edinburgh Health Economics research groups are running the Data Science, Pathway Analysis and Health Economic Modelling as part of the UK HER2-RADICAL Trial.
The trial is funded by the NIHR Health Technology Assessment programme and is co-ordinated by the Institute of Cancer Research Clinical Trials Unit.
Treatment of HER2 positive early breast cancer involves severe patient side effects and high NHS costs
The presence or absence of residual disease following neoadjuvant systemic anti-cancer therapy (neoSACT) for HER2-positive early breast cancer (HER2+ EBC) provides powerful prognostic information that may guide subsequent adjuvant treatment for the individual patient.
Pathological complete response (pCR) following neoSACT identifies a population with excellent outcomes in whom the balance of toxicity associated with the current non-response-adapted treatment pathway may be disproportionate to the absolute clinical benefit.
HER2-RADiCAL seeks to reduce the burden of toxicity and NHS cost of treating HER2+ EBC by testing the hypothesis that pCR can be used as a functional response biomarker to select patients who can safely receive less intensive therapy, with minimal or no loss of efficacy in the population.
HER2-RADiCAL is a response-directed interventional cohort (single-arm) study embedded within a real-world data driven clinical pathway model. Participants will be registered within 6 weeks of completion of breast cancer surgery. The main eligibility criteria include clinical stage T1N1 or T2N0-1 at diagnosis and locally-determined pCR (ypT0/Tis ypN0) after standard of care taxane-based (non-anthracycline) neoadjuvant chemotherapy, trastuzumab and pertuzumab. After registration participants will continue to receive trastuzumab to complete a total of 9 cycles including those (neo-)adjuvant cycles administered prior to study entry. Participants will receive no further pertuzumab or adjuvant chemotherapy.
The primary clinical endpoint is relapse free interval. Recruitment of 720 participants over 3 years will provide 90% power to exclude an event rate >6.5% at 3 years. Secondary endpoints include relapse-free survival, invasive breast cancer-free survival, invasive disease-free survival, distant recurrence-free interval, breast cancer-free interval, treatment pathway adherence and cost-effectiveness. Health economic modelling will compare the protocol-driven study cohort with two comparator pathways: a non-response adapted maximum therapy pathway (the standard clinical pathway prior to the study) and a real-world representative pathway taken from 4-nation NHS data at the beginning and end of the study.
Patient advocates have been involved in study design and will have an ongoing key role in overseeing the progress of the study as members of the Trial Management Group.
HER2-RADiCAL is running at approximately 40 UK sites commenced in December 2021.