Abstract OT1-06-01: OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer

RC Stein, A Makris, L Hughes-Davies, IR Macpherson, PS Hall, DA Cameron, HM Earl, SE Pinder, CJ Poole, DW Rea, S McIntosh, V Harmer, A Morgan, L Rooshenas, C Conefrey, JL Donovan, C Hulme, C McCabe, N Stallard, A CampbellH Higgins, JMS Bartlett, A Marshall, JA Dunn

Research output: Contribution to conferenceAbstract

Abstract

Abstracts: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TexasBackground: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk in hormone-sensitive HER2-negative node-negative early breast cancer, allowing patients with low risk to safely avoid chemotherapy. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) aims to validate MPA's as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population.Methods: OPTIMA is a partially blinded multi-center, phase 3 randomized controlled trial with an adaptive two-stage design. The main eligibility criteria are women or men aged 40 or older with resected ER-positive, HER2-negative breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment. Those with a “high risk” tumor MPA score receive standard management whilst those at “low risk” are treated with endocrine therapy alone. The preliminary phase (OPTIMA prelim) evaluated the performance of several MPAs to select a test to be used in the main efficacy trial based on economic analysis, and assessed the feasibility and acceptability of a large UK trial. OPTIMA prelim used Oncotype DX as the primary discriminator; the main trial will use Prosigna (PAM50) with Prosigna Score ≤60 defined as “low-risk”. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed therapy. Secondary outcomes include IDFS in “low-risk” patients, quality of life and additional survival measures. An integrated qualitative recruitment study will identify and address challenges to recruitment and informed consent. Tumor blocks from all consenting participants will be banked allowing the performance of alternative MPA technologies to be evaluated. Recruitment of 4500 patients will permit demonstration of 3% non-inferiority of test-directed treatment, with 5% significance and 85% power, assuming 3 years follow-up and a control arm 5-year IDFS of at least 85%. The addition of patients from OPTIMA prelim will allow non-inferiority to be assessed with 2.5% significance.Results: OPTIMA-prelim recruited 412 patients in 23 months from 35 sites with a 47% acceptance rate. The main study opened in January 2017. Early progress indicates that the recruitment target is achievable in the intended 46-month timescale through the participation of >100 sitesConclusion: OPTIMA, as one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer, is expected to have a global impact on breast cancer treatment. Experience from OPTIMA prelim showed that patient advocate support and close engagement with sites will aid trial success.Funding: The project is funded in the UK by the 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.Citation Format: Stein RC, Makris A, Hughes-Davies L, Macpherson IR, Hall PS, Cameron DA, Earl HM, Pinder SE, Poole CJ, Rea DW, McIntosh S, Harmer V, Morgan A, Rooshenas L, Conefrey C, Donovan JL, Hulme C, McCabe C, Stallard N, Campbell A, Higgins H, Bartlett JMS, Marshall A, Dunn JA. OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-01.
Original languageEnglish
Publication statusPublished - 15 Feb 2018
Event2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; - Texas, San Antonio, United States
Duration: 05 Dec 201709 Dec 2017

Conference

Conference2017 San Antonio Breast Cancer Symposium; December 5-9, 2017;
CountryUnited States
City San Antonio
Period05/12/201709/12/2017

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Cost-Benefit Analysis
Breast Neoplasms
Gene Expression
Drug Therapy
Disease-Free Survival
Therapeutics
Neoplasms
Random Allocation
Informed Consent
Patient Selection
Randomized Controlled Trials
Lymph Nodes
Economics
Quality of Life
Hormones
Technology
Survival
Population

Cite this

Stein, RC., Makris, A., Hughes-Davies, L., Macpherson, IR., Hall, PS., Cameron, DA., ... Dunn, JA. (2018). Abstract OT1-06-01: OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer. Abstract from 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017;, San Antonio, United States.
Stein, RC ; Makris, A ; Hughes-Davies, L ; Macpherson, IR ; Hall, PS ; Cameron, DA ; Earl, HM ; Pinder, SE ; Poole, CJ ; Rea, DW ; McIntosh, S ; Harmer, V ; Morgan, A ; Rooshenas, L ; Conefrey, C ; Donovan, JL ; Hulme, C ; McCabe, C ; Stallard, N ; Campbell, A ; Higgins, H ; Bartlett, JMS ; Marshall, A ; Dunn, JA. / Abstract OT1-06-01: OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer. Abstract from 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017;, San Antonio, United States.
@conference{d7c1adb291f04f54af4660721d87b109,
title = "Abstract OT1-06-01: OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer",
abstract = "Abstracts: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TexasBackground: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk in hormone-sensitive HER2-negative node-negative early breast cancer, allowing patients with low risk to safely avoid chemotherapy. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) aims to validate MPA's as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population.Methods: OPTIMA is a partially blinded multi-center, phase 3 randomized controlled trial with an adaptive two-stage design. The main eligibility criteria are women or men aged 40 or older with resected ER-positive, HER2-negative breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment. Those with a “high risk” tumor MPA score receive standard management whilst those at “low risk” are treated with endocrine therapy alone. The preliminary phase (OPTIMA prelim) evaluated the performance of several MPAs to select a test to be used in the main efficacy trial based on economic analysis, and assessed the feasibility and acceptability of a large UK trial. OPTIMA prelim used Oncotype DX as the primary discriminator; the main trial will use Prosigna (PAM50) with Prosigna Score ≤60 defined as “low-risk”. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed therapy. Secondary outcomes include IDFS in “low-risk” patients, quality of life and additional survival measures. An integrated qualitative recruitment study will identify and address challenges to recruitment and informed consent. Tumor blocks from all consenting participants will be banked allowing the performance of alternative MPA technologies to be evaluated. Recruitment of 4500 patients will permit demonstration of 3{\%} non-inferiority of test-directed treatment, with 5{\%} significance and 85{\%} power, assuming 3 years follow-up and a control arm 5-year IDFS of at least 85{\%}. The addition of patients from OPTIMA prelim will allow non-inferiority to be assessed with 2.5{\%} significance.Results: OPTIMA-prelim recruited 412 patients in 23 months from 35 sites with a 47{\%} acceptance rate. The main study opened in January 2017. Early progress indicates that the recruitment target is achievable in the intended 46-month timescale through the participation of >100 sitesConclusion: OPTIMA, as one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer, is expected to have a global impact on breast cancer treatment. Experience from OPTIMA prelim showed that patient advocate support and close engagement with sites will aid trial success.Funding: The project is funded in the UK by the 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.Citation Format: Stein RC, Makris A, Hughes-Davies L, Macpherson IR, Hall PS, Cameron DA, Earl HM, Pinder SE, Poole CJ, Rea DW, McIntosh S, Harmer V, Morgan A, Rooshenas L, Conefrey C, Donovan JL, Hulme C, McCabe C, Stallard N, Campbell A, Higgins H, Bartlett JMS, Marshall A, Dunn JA. OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-01.",
author = "RC Stein and A Makris and L Hughes-Davies and IR Macpherson and PS Hall and DA Cameron and HM Earl and SE Pinder and CJ Poole and DW Rea and S McIntosh and V Harmer and A Morgan and L Rooshenas and C Conefrey and JL Donovan and C Hulme and C McCabe and N Stallard and A Campbell and H Higgins and JMS Bartlett and A Marshall and JA Dunn",
year = "2018",
month = "2",
day = "15",
language = "English",
note = "2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; ; Conference date: 05-12-2017 Through 09-12-2017",

}

Stein, RC, Makris, A, Hughes-Davies, L, Macpherson, IR, Hall, PS, Cameron, DA, Earl, HM, Pinder, SE, Poole, CJ, Rea, DW, McIntosh, S, Harmer, V, Morgan, A, Rooshenas, L, Conefrey, C, Donovan, JL, Hulme, C, McCabe, C, Stallard, N, Campbell, A, Higgins, H, Bartlett, JMS, Marshall, A & Dunn, JA 2018, 'Abstract OT1-06-01: OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer', 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017;, San Antonio, United States, 05/12/2017 - 09/12/2017.

Abstract OT1-06-01: OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer. / Stein, RC; Makris, A; Hughes-Davies, L; Macpherson, IR; Hall, PS; Cameron, DA; Earl, HM; Pinder, SE; Poole, CJ; Rea, DW; McIntosh, S; Harmer, V; Morgan, A; Rooshenas, L; Conefrey, C; Donovan, JL; Hulme, C; McCabe, C; Stallard, N; Campbell, A; Higgins, H; Bartlett, JMS; Marshall, A; Dunn, JA.

2018. Abstract from 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017;, San Antonio, United States.

Research output: Contribution to conferenceAbstract

TY - CONF

T1 - Abstract OT1-06-01: OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer

AU - Stein, RC

AU - Makris, A

AU - Hughes-Davies, L

AU - Macpherson, IR

AU - Hall, PS

AU - Cameron, DA

AU - Earl, HM

AU - Pinder, SE

AU - Poole, CJ

AU - Rea, DW

AU - McIntosh, S

AU - Harmer, V

AU - Morgan, A

AU - Rooshenas, L

AU - Conefrey, C

AU - Donovan, JL

AU - Hulme, C

AU - McCabe, C

AU - Stallard, N

AU - Campbell, A

AU - Higgins, H

AU - Bartlett, JMS

AU - Marshall, A

AU - Dunn, JA

PY - 2018/2/15

Y1 - 2018/2/15

N2 - Abstracts: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TexasBackground: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk in hormone-sensitive HER2-negative node-negative early breast cancer, allowing patients with low risk to safely avoid chemotherapy. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) aims to validate MPA's as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population.Methods: OPTIMA is a partially blinded multi-center, phase 3 randomized controlled trial with an adaptive two-stage design. The main eligibility criteria are women or men aged 40 or older with resected ER-positive, HER2-negative breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment. Those with a “high risk” tumor MPA score receive standard management whilst those at “low risk” are treated with endocrine therapy alone. The preliminary phase (OPTIMA prelim) evaluated the performance of several MPAs to select a test to be used in the main efficacy trial based on economic analysis, and assessed the feasibility and acceptability of a large UK trial. OPTIMA prelim used Oncotype DX as the primary discriminator; the main trial will use Prosigna (PAM50) with Prosigna Score ≤60 defined as “low-risk”. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed therapy. Secondary outcomes include IDFS in “low-risk” patients, quality of life and additional survival measures. An integrated qualitative recruitment study will identify and address challenges to recruitment and informed consent. Tumor blocks from all consenting participants will be banked allowing the performance of alternative MPA technologies to be evaluated. Recruitment of 4500 patients will permit demonstration of 3% non-inferiority of test-directed treatment, with 5% significance and 85% power, assuming 3 years follow-up and a control arm 5-year IDFS of at least 85%. The addition of patients from OPTIMA prelim will allow non-inferiority to be assessed with 2.5% significance.Results: OPTIMA-prelim recruited 412 patients in 23 months from 35 sites with a 47% acceptance rate. The main study opened in January 2017. Early progress indicates that the recruitment target is achievable in the intended 46-month timescale through the participation of >100 sitesConclusion: OPTIMA, as one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer, is expected to have a global impact on breast cancer treatment. Experience from OPTIMA prelim showed that patient advocate support and close engagement with sites will aid trial success.Funding: The project is funded in the UK by the 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.Citation Format: Stein RC, Makris A, Hughes-Davies L, Macpherson IR, Hall PS, Cameron DA, Earl HM, Pinder SE, Poole CJ, Rea DW, McIntosh S, Harmer V, Morgan A, Rooshenas L, Conefrey C, Donovan JL, Hulme C, McCabe C, Stallard N, Campbell A, Higgins H, Bartlett JMS, Marshall A, Dunn JA. OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-01.

AB - Abstracts: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TexasBackground: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk in hormone-sensitive HER2-negative node-negative early breast cancer, allowing patients with low risk to safely avoid chemotherapy. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) aims to validate MPA's as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population.Methods: OPTIMA is a partially blinded multi-center, phase 3 randomized controlled trial with an adaptive two-stage design. The main eligibility criteria are women or men aged 40 or older with resected ER-positive, HER2-negative breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment. Those with a “high risk” tumor MPA score receive standard management whilst those at “low risk” are treated with endocrine therapy alone. The preliminary phase (OPTIMA prelim) evaluated the performance of several MPAs to select a test to be used in the main efficacy trial based on economic analysis, and assessed the feasibility and acceptability of a large UK trial. OPTIMA prelim used Oncotype DX as the primary discriminator; the main trial will use Prosigna (PAM50) with Prosigna Score ≤60 defined as “low-risk”. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed therapy. Secondary outcomes include IDFS in “low-risk” patients, quality of life and additional survival measures. An integrated qualitative recruitment study will identify and address challenges to recruitment and informed consent. Tumor blocks from all consenting participants will be banked allowing the performance of alternative MPA technologies to be evaluated. Recruitment of 4500 patients will permit demonstration of 3% non-inferiority of test-directed treatment, with 5% significance and 85% power, assuming 3 years follow-up and a control arm 5-year IDFS of at least 85%. The addition of patients from OPTIMA prelim will allow non-inferiority to be assessed with 2.5% significance.Results: OPTIMA-prelim recruited 412 patients in 23 months from 35 sites with a 47% acceptance rate. The main study opened in January 2017. Early progress indicates that the recruitment target is achievable in the intended 46-month timescale through the participation of >100 sitesConclusion: OPTIMA, as one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer, is expected to have a global impact on breast cancer treatment. Experience from OPTIMA prelim showed that patient advocate support and close engagement with sites will aid trial success.Funding: The project is funded in the UK by the 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.Citation Format: Stein RC, Makris A, Hughes-Davies L, Macpherson IR, Hall PS, Cameron DA, Earl HM, Pinder SE, Poole CJ, Rea DW, McIntosh S, Harmer V, Morgan A, Rooshenas L, Conefrey C, Donovan JL, Hulme C, McCabe C, Stallard N, Campbell A, Higgins H, Bartlett JMS, Marshall A, Dunn JA. OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-01.

M3 - Abstract

ER -

Stein RC, Makris A, Hughes-Davies L, Macpherson IR, Hall PS, Cameron DA et al. Abstract OT1-06-01: OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer. 2018. Abstract from 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017;, San Antonio, United States.