Abstract P1-14-06: A phase II randomized study with eribulin/cyclophosphamide (ErC) and docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in HER2-negative breast cancer- Final analysis of primary endpoint and correlative analysis results

Background : Eribulin mesylate (Er) is a non-taxane inhibitor of microtubule growth that results in G2-M cell cycle arrest, disruption of normal mitotic spindles and apoptosis. Er demonstrated an overall survival (OS) but not progression free survival (PFS) advantage in anthracycline and taxane refractory breast cancer pts. This OS rather than PFS benefit has been attributed to Er9s potential to suppress new metastases through its effects on the epithelial mesenchymal transition (EMT) pathway, even in the absence of an effect on the primary tumor or established metastases. In this study ErC was compared to TC, a standard regimen for (neo) adjuvant treatment. A companion exploratory analysis examined the EMT markers E-cadherin and vimentin, as well as the endothelial marker CD-31 assessing tumor vasculature. Final assessments of the primary endpoint of pathological complete response (pCR) and results of the correlative studies will be presented. Methods: Women with histologically confirmed invasive HER2-negative (IHC 0-1+ or FISH/SISH negative), cT1-3, cN0-2, M0 (pN3a disease allowed) adenocarcinoma of the breast were eligible. Following a 10 pt lead-in to confirm the safety/feasibility of ErC, pts were randomized 2:1. Arm 1, Er 1.4 mg/m 2 IV (Days 1 & 8) and C 600 mg/m 2 IV (Day 1); Arm 2, T 75 mg/m 2 IV and C 600 mg/m 2 IV on Day 1, both regimens administered q 21 days x 6 cycles followed by surgery. Tumor samples were collected at baseline and from residual breast cancer at the time of surgery. Samples were assayed for E-cadherin, vimentin, and CD-31 expression by immunohistochemistry. Results: Enrollment was completed 4/2014 (76 pts); 10 pts in lead-in phase, 66 pts were randomized (Arm 1, 44; Arm 2, 22). In the randomized population, 77% had invasive ductal adenocarcinoma; median tumor size 3.1 cm (range, 0.4-10cm; 29.5% were T3); axillary nodes clinically positive in 52%. 34% of pts were triple negative (TN). 59 pts (89%) underwent surgery after receiving neoadjuvant chemotherapy (NAC) on study. pCR rates were 9% and 18% on the TC and ErC arms respectively. 4/7 pts with pCR on the ErC arm were TN. tumor samples were analyzed from 69 pts (including lead-in pts) for expression of the EMT biomarkers. Of these, 40 pts had paired pre- and post-treatment samples, and 29 pts had either a pre- or post-treatment sample (including 8 pre-treatment samples from pts who achieved pCR). In pre-treatment tumor specimens (61 samples), E-cadherin levels were modest-high in 80%, vimentin expression was seen in 39%, and CD-31 expression observed in 21% of the samples. Analysis of pre- and post-treatment paired specimens and differential effects according to treatment regimen will be presented. Conclusion: The observed pCR rate of 18% with ErC in this HER2- pt population was comparable with other NAC regimens. Correlative evaluation of EMT markers and tumor vascular density with response is ongoing and will be presented. Citation Format: Yardley DA, Chandra P, Hart L, Wright GS, Ward P, Mani A, Shastry M, Finney L, Guo S, DeBusk LM, Hainsworth JD, Burris III HA. A phase II randomized study with eribulin/cyclophosphamide (ErC) and docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in HER2-negative breast cancer- Final analysis of primary endpoint and correlative analysis results. [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 P1-14-06.