OPTIMA (Optimal Personalised Treatment of early breast cancer using Multi-parameter Analysis): A prospective trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions

Adele Francis, Robert C. Stein, Andrea Marshall, Daniel W. Rea, David A. Cameron, Iain R. Macpherson, Helena M. Earl, Christopher J. Poole, Peter S. Hall, John M.S. Bartlett, Leila Rooshenas, Adrienne Morgan, Victoria Harmer, Jenny Donovan, Claire Hulme, Christopher McCabe, Sarah E. Pinder, Luke Hughes-Davies, Andreas Makris, Janet A. Dunn

Research output: Contribution to journalArticle (Academic Journal)

Abstract

Introduction: 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 MPAs to predict chemotherapy sensitivity in a largely node-positive breast cancer population.

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.)
Original languageEnglish
Pages (from-to)S9-S10
Number of pages2
JournalEuropean Journal of Surgical Oncology
Volume42
Issue number5
Early online date9 Apr 2016
DOIs
Publication statusPublished - May 2016

Structured keywords

  • Centre for Surgical Research

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    Francis, A., Stein, R. C., Marshall, A., Rea, D. W., Cameron, D. A., Macpherson, I. R., Earl, H. M., Poole, C. J., Hall, P. S., Bartlett, J. M. S., Rooshenas, L., Morgan, A., Harmer, V., Donovan, J., Hulme, C., McCabe, C., Pinder, S. E., Hughes-Davies, L., Makris, A., & Dunn, J. A. (2016). OPTIMA (Optimal Personalised Treatment of early breast cancer using Multi-parameter Analysis): A prospective trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions. European Journal of Surgical Oncology, 42(5), S9-S10. https://doi.org/10.1016/j.ejso.2016.02.048