OPTIMA: a prospective randomised trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions
Session type: Poster / e-Poster / Silent Theatre session
Theme: Diagnosis and therapy
Multi-parameter gene expression assays (MPAs) are used to estimate individuals’ residual risk and guide chemotherapy use in hormone-sensitive HER2-negative node-negative early breast cancer. OPTIMA aims to prospectively validate the use of MPA testing to additionally predict chemotherapy sensitivity in a largely node-positive breast cancer population.
OPTIMA is a partially blinded multi-centre, phase 3 RCT with an adaptive two-stage design. The preliminary phase (OPTIMA-prelim) evaluated the performance of MPAs for use in the main efficacy trial and assessed the feasibility and acceptability of a large UK trial. It demonstrated that a large-scale study is feasible in the UK. It showed that research on MPA-directed therapy, especially with Prosigna, should be of substantial value to the NHS. The OPTIMA patient population is women aged ≥40 years or men with resected early stage ER-positive, HER2-negative breast cancer, who have either 1-9 involved nodes or tumours ≥30mm. Randomisation is to standard management (chemotherapy then endocrine therapy) or MPA-directed treatment. Those with a tumour categorised as “high-risk” by the test have standard management whilst those at “low-risk” receive endocrine therapy alone. OPTIMA-prelim used Oncotype DX as the discriminator; OPTIMA uses Prosigna (PAM50). Co-primary outcomes are invasive disease free survival and cost-effectiveness. Tumour blocks from all consenting participants will be banked allowing the performance of alternative MPA technologies to be evaluated. An integrated qualitative study, undertaken with support from theme II of the MRC ConDuCT-II methodology hub, will aim to optimise recruitment and informed consent. A 4500 patient study allows the demonstration of 3% non-inferiority of MPA-directed treatment with 5% significance and 85% power. Inclusion of OPTIMA-prelim patients allows assessment of non-inferiority with 2.5% significance.
Recruitment commenced in 2016.
OPTIMA is a prospective RCT validating MPA-directed therapy in node-positive hormone-sensitive early breast cancer and will have a global impact on patient treatment.