Abstract OT2-01-20: Phase IIB study of neoadjuvant panitumumab combined with carboplatin and paclitaxel (PaCT) for anthracycline-resistant triple-negative breast cancer (TNBC)
Authors: Lim B , Helgason T , Hess KR , Piwnica-Worms H , Yang W , Adrada BE , Rauch GM , Gilcrease M , Symmans FW , Huo L , Mittendorf EA , Thompson A , Stacy M-TL , Debu T , Ueno NT 
Published: March 2017

Abstract
BACKGROUND: Approximately 50% of patients with TNBC treatedwithstandardtaxane/anthracycline-based neoadjuvant chemotherapy (NACT)have chemo-insensitive disease (CID), i.e., residual disease burden (RCB)-II/III at the time of surgery, and 40-80% of patients develop recurrence within 3 years. Recent developments in molecular profiling have identified subsets of TNBC with distinct, targetable molecular features. We developed a clinical trial to identify and characterize CID (ARTEMIS: A Randomized, TNBC-Enrolling trial to confirm Molecular profiling Improves Survival). In ARTEMIS, patients with localized TNBC will undergo a pretreatment biopsy, then begin anthracycline-based NACT. During NACT, we use molecular profiling and response assessment to identify CID and allocate patients to alternative therapies to overcome CID. Epidermal growth factor receptor (EGFR) is overexpressed in 25-30% of TNBC. In preclinical studies, suppression of EGFR signaling has shown efficacy in controlling cancers through suppression of the stem cell population, enhanced apoptosis via MAPK/PI3K signaling, and modulation of epithelial-mesenchymal transition (EMT). Moreover, in a phase II trial of triple negative inflammatory breast cancer, neoadjuvant PaCT yielded significantly higher pathologic complete response (pCR) rates than historic control. Taken together, we hypothesize that using PaCT to suppress EGFR in TNBC will enhance the pCR rate.
OBJECTIVES: Primary objective: determine pCR and RCB-0/I rates in TNBC patients with CID given PaCT. Secondary objective: determine the benefit of using baseline genomic signatures to develop an alternative second phase of NACT.
TRIAL DESIGN AND STATISTICAL METHODS: Patients with &gt;10% volume reduction for non-CID or &lt;80% for CID will enroll in a biomarker-guided, experimental, nonrandomized phase II study and be given PaCT (panitumumab 2.5 mg/kg, carboplatin AUC 5, paclitaxel 80 mg/m2). Because pCR rates in pts with CID with additional cycles of taxane-based therapy are low (∼5%), a 20% response rate (RCB-0 or RCB-I) will be considered clinically meaningful. A two-stage Gehan-type design will be employed. If at least 1 of 14 patients responds, 23 more patients will be added, for a total of 37 patients. This design has a 49% chance of terminating after the first stage if the true response rate is 0.05, 23% if the rate is 0.10, 10% if the rate is 0.15, and 4% if the rate is 0.20. If accrual continues to the second stage and 37 patients are enrolled, the 95% confidence interval for a 0.20 response rate will be 0.10 to 0.35.
BRIEF ELIGIBILITY CRITERIA: Inclusion: localized TNBC; enrolled in ARTEMIS trial; adequate organ, bone marrow, and cardiac parameters; Exclusion: pregnant or lactating, known or suspected metastasis.
CORRELATIVE SCIENCE: Circulating tumor cells (CTCs) and cell free (cf) DNA in baseline and subsequent blood samples, EGFR expression (immunohistochemistry), stem cell/EMT/apoptosis marker changes in tissue and CTCs, PD-L1 glycosylation for EGFR sensitivity.
Citation Format: Lim B, Helgason T, Hess KR, Piwnica-Worms H, Yang W, Adrada BE, Rauch GM, Gilcrease M, Symmans FW, Huo L, Mittendorf EA, Thompson A, Stacy M-TL, Debu T, Ueno NT. Phase IIB study of neoadjuvant panitumumab combined with carboplatin and paclitaxel (PaCT) for anthracycline-resistant triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-20.