Methods: Eligible patients are men or women aged ≥40 years 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” have endocrine therapy alone. 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 trial. OPTIMA-prelim used Oncotype DX as the primary discriminator; OPTIMA will use Prosigna (PAM50). Co-primary outcomes are invasive disease free survival and cost-effectiveness. A 4500 patient study allows the demonstration of 3% non-inferiority of test-directed treatment with 5% significance and 85% power. Addition of OPTIMA-prelim patients allows assessment of non-inferiority with 2.5% significance.
Results: OPTIMA-prelim demonstrated that a large-scale UK study is feasible. It showed that research on MPA-directed therapy, especially with Prosigna, should be of substantial value to the NHS.
Conclusion: OPTIMA is a large prospective trial validating test-directed therapy in node-positive hormone-sensitive early breast cancer and will have a global impact. OPTIMA opens to recruitment in February 2016.
(Funded by NIHR HTA, 10/34/501. Views expressed are those of authors.)
- Centre for Surgical Research