OPTIMA, a prospective randomised trial to validate the clinical and economic utility of tumour gene expression test use for prediction of chemotherapy sensitivity in high-risk early breast cancer


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Rob Stein1,Andreas Makris2,Luke Hughes-Davies3,Iain Macpherson4,Andrea Marshall5,Georgina Dotchin5,Peter Hall6,David Cameron6,Bjørn Naume7,Helena Earl8,Stuart McIntosh9,Sarah Pinder10,Jeremy Thomas6,Christopher Poole11,Daniel Rea12,John Bartlett13,Adrienne Morgan14,Leila Rooshenas15,Carmel Conefrey15,Jenny Donovan15,Claire Hulme16,Victoria Harmer17,Helen Higgins5,Janet Dunn5
1UCL,2Mount Vernon Cancer Centre, East and North Hertfordshoire NHS Trust,3Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust,4University of Glasgow,5University of Warwick,6University of Edinburgh,7Oslo University Hospital,8Cambridge University Hospitals,9Queen's University, Belfast,10King's College London,11University Hospitals Coventry and Warwickshire NHS Trust,12University of Birmingham,13Ontario Institute for Cancer Research MaRS Centre,14ICPV,15University of Bristol,16University of Leeds,17Imperial College Healthcare NHS Trust

Abstract

Background

Multi-parameter tumour gene expression assays (MPA’s) are widely used to estimate individual patient prognosis and to guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a low-risk node negative population. OPTIMA will investigate the ability of MPA’s to predict chemotherapy sensitivity in a largely node-positive population where evidence is lacking.

Method

OPTIMA is a partially blinded multi-centre RCT with an adaptive two-stage design. The main eligibility criteria are patients aged 40 or older with resected ER-positive, HER2-negative breast cancer and up to 9 involved axillary lymph nodes. Randomisation is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a tumour Prosigna Score (PS) >60 receive standard management whilst those with PS ≤60 are treated with endocrine therapy alone. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed treatment. Secondary outcomes include IDFS in patients with low-PS tumours and quality of life. An integrated qualitative recruitment study addresses challenges to consent and recruitment. Tumour blocks will be banked to allow evaluation of alternative MPA technologies. Recruitment of 4500 patients over 5 years will permit demonstration of 3% non-inferiority of test-directed treatment. Inclusion of 412 patients from the preliminary study will allow non-inferiority to be assessed with 2.5% significance.

Results

The OPTIMA main trial opened in January 2017. Overall recruitment will reach 1000 in August 2018.  Recruitment in Norway will commence in July 2018.

Conclusion

OPTIMA is expected to have a global impact on the treatment of node-positive breast cancer. Experience from the preliminary study and engagement with centres will aid trial success.

OPTIMA is funded by the UK NIHR HTA Programme (10/34/501). Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the DoH.