Abstract OT2-03-03: Women's triple-negative, first-line treatment: Improving outcomes in triple-negative breast cancer using molecular triaging and diagnostic imaging to guide neoadjuvant therapy
Authors: Mitri ZI , Ueno NT , Yang W , Valero V , Litton JK , Murthy RK , Ibrahim NK , Arun BK , Mittendorf EA , Hunt KK , Meric-Bernstam F , Thompson A , Piwnica-Worms H , Tripathy D , Symmans F , Moulder-Thompson S 
Published: May 2016

Abstract
BACKGROUND:
In triple negative breast cancer (TNBC), pathologic compete response/residual cancer burden-0 (pCR/RCB-0) or minimal residual disease (RCB-I) following neoadjuvant chemotherapy (NACT) is associated with a good prognosis. This is in contrast to extensive residual disease (RCB-II-III) which carries approximately a 50% chance of recurrence. These patients have a particularly poor prognosis as there are currently no targeted agents to salvage chemoresistant disease. It is important to predict pCR in order to direct responsive disease toward standard NACT and non-responsive disease (NRD) to therapy on clinical trials.
TRIAL DESIGN:
The use of genomic signatures (JAMA, 2011; 305:1873-81) and imaging to predict response to NACT will be validated, and the clinical impact of selecting patients with predicted NRD for targeted therapy on clinical trial will be determined. Patients will undergo primary tumor biopsy for molecular profiling and will be randomized 2:1 to know the results versus not (control). Following that, all patients will receive 4 cycles of anthracycline-based NACT, with imaging used for response assessment. Patients with molecular/imaging criteria for NRD will be offered enrollment on a clinical trial based upon molecular profiling or based upon physician/patient choice (control).
INCLUSION CRITERIA:
Tumor size ≥1.5 cm diameter; TNBC by standard assays; ≥18 years of age; LVEF ≥50%; adequate organ and bone marrow function
EXCLUSION CRITERIA:
Stage IV disease; invasive cancer within 5 years; excisional biopsy of the primary tumor; features that limit response assessment by imaging; unfit for taxane and/or antracycline regimens; prior anthracycline therapy; ≥grade II neuropathy; Zubrod performance status of ≥2; history of serious cardiac events
PRIMARY AIM:
- Prospectively determine the impact of a molecular diagnostic/imaging platform in patients with localized invasive TNBC
SECONDARY AIMS:
- Compare rates of clinical trial enrollment
- Evaluate disease free survival in the experimental arms compared to control standard NACT
- Perform integrated biomarker analyses and identify therapeutic targets for resistant disease
STATISTICAL METHODS:
A maximum of 360 patients will be randomized (2:1)using a group sequential design with one-sided O'Brien-Fleming boundaries, with two equally spaced binding interim tests for futility and superiority and one final test, having an overall Type I error .05 and power .80 to detect an improvement in pCR/RCB-I from 50% to 64%.
Citation Format: Mitri ZI, Ueno NT, Yang W, Valero V, Litton JK, Murthy RK, Ibrahim NK, Arun BK, Mittendorf EA, Hunt KK, Meric-Bernstam F, Thompson A, Piwnica-Worms H, Tripathy D, Symmans F, Moulder-Thompson S. Women's triple-negative, first-line treatment: Improving outcomes in triple-negative breast cancer using molecular triaging and diagnostic imaging to guide neoadjuvant therapy. [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 OT2-03-03.