Abstract OT3-02-12: 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
Notice bibliographique
Résumé
Abstract Background: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk and to guide chemotherapy use in hormone-sensitive HER2-negative node-negative early breast cancer. These uses of MPAs have not yet been prospectively validated. OPTIMA aims to validate the use of MPA testing to predict 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 preliminary phase (OPTIMA prelim) evaluated the performance of MPAs to identify a suitable test(s) to be used in the main efficacy trial and assessed the feasibility and acceptability of a large UK trial. Eligible patients are men or women aged 40 years or older who have surgically resected early stage breast cancer, which is ER-positive and HER2-negative and who have either 1-9 involved axillary lymph nodes or tumors of at least 30mm diameter. Randomization is to standard management (chemotherapy followed by endocrine therapy) or to MPA-directed treatment. Those with a tumor categorized as "high-risk" by the test will be assigned to standard management whilst those at "low-risk" will be treated with endocrine therapy alone. OPTIMA prelim used Oncotype DX as the primary discriminator; the main trial will use Prosigna (PAM50). The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed therapy compared to standard practice. Secondary outcomes include IDFS in "low-risk" patients, distant disease free survival, breast cancer specific survival, overall survival and quality of life. 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 over 4 years 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. It confirmed the acceptability of randomization to patients with a 47% acceptance rate, and to clinicians and hence the feasibility of a large prospective trial of test-directed treatment running in 100-plus UK sites. It showed that investment into research on test-directed therapy, especially with Prosigna, should be of substantial value to the NHS. Conclusion: OPTIMA, as one of two large scale prospective trials validating the use of test-guided chemotherapy in node-positive hormone-sensitive early breast cancer will have a global impact on patient treatment. Recruitment into the main efficacy trial will commence in October 2015. Funding: Project 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. Citation Format: Stein RC, Marshall A, Hall PS, Bartlett JMS, Rooshenas L, Campbell A, Cameron DA, Rea D, Macpherson I, Earl HM, Poole CJ, Francis A, Morgan A, Harmer V, Pinder SE, Stallard N, Donovan J, Hulme C, McCabe C, Hughes-Davies L, Makris A, Dunn JA. 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. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-12.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».