NeoTAILOR: A Phase II Biomarker-directed Approach to Guide Neoadjuvant Therapy for Patients With Stage II/III ER-positive, HER2-negative Breast Cancer
Summary
This study aims to utilize a novel biomarker-driven approach to guide neoadjuvant treatment selection. It is the hypothesis that this will improve clinical response for postmenopausal women with clinical stage II/III ER-positive, HER2-negative breast cancer and identify those who may not require neoadjuvant chemotherapy, with a primary focus on outcomes in Black patients.
Detailed description
Risk category is defined as follows: * Low risk: * Baseline Ki67 ≤ 10% (OR) * Luminal A molecular intrinsic subtype by PAM50 * High risk: * Non-Luminal A molecular intrinsic subtype by PAM50 (OR) * In cases of non-diagnostic PAM50 molecular intrinsic subtype, patients will enroll in the high-risk group and undergo Week 4 tumor biopsy.
Arms & interventions
- DeviceVENTANA MIB-1 Ki67 assay
Ki67 scoring determination (standard of care) utilizing the Ki67 MIB-1 assay (clone 30-9) (VENTANA) will be performed at baseline, Week 4 (+/- 14 days - high-risk group only), and at time of surgery in accordance with the International Ki67 in Breast Cancer Working Group guidelines.
- DeviceOncotype DX® Recurrence Score
Oncotype DX® Recurrence Score (RS) testing - assessing expression of 21 genes including 16 cancer-related genes and 5 reference genes - will be performed as standard of care in a central laboratory (Exact Sciences) on RNA extracted from formalin-fixed paraffin-embedded core-biopsy samples.
- DevicePAM50-based Prosigna breast cancer gene signature assay
This PAM50-based Prosigna breast cancer gene signature assay for intrinsic molecular subtype determination will be performed on formalin-fixed, paraffin-embedded (FFPE) core-biopsy samples.
- DrugAnastrozole
Standard of care. All patients must start on anastrozole at time of enrollment but may switch to another aromatase inhibitor (letrozole or exemestane) due to toxicity or financial/other concerns at discretion of investigator after a discussion with the PI. Every effort to minimize interruption of aromatase inhibitor (AI) therapy is recommended.
- DrugCombination anthracycline and/or taxane based treatment
Standard of care
Outcome measures
Primary
Objective response rate (ORR) by breast MRI in the combined low-risk plus high-risk endocrine-sensitive groups (pooled endocrine therapy-responders)
* ORR is defined as patients achieving clinical complete response (CR) or partial response (PR) according to RECIST v1.1. * Complete Response (CR): disappearance of all target and non-target lesions. Residual lesions thought to be non-malignant should be further investigated before CR can be accepted. * Partial Response (PR): ≥30% decrease in the sum of measures of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD.
Time frame: Through completion of treatment (estimated to be 6 months)
Secondary
Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment
Time frame: Through completion of surgery (estimated to be 6 months)
Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment
Time frame: Through completion of surgery (estimated to be 6 months)
Objective response rate (ORR) by breast MRI in the high-risk endocrine-sensitive group
Time frame: Through completion of treatment (estimated to be 6 months)
Objective response rate (ORR) by breast MRI in the high-risk endocrine-resistant group (high risk patients with week 4 Ki67 > 10% post anastrozole)
Time frame: Through completion of treatment (estimated to be 6 months)
Eligibility criteria
Study locations (1)
Washington University School of Medicine
St Louis, Missouri, 63110