Abstract OT2-02-03: Pilot study of zirconium-89 bevacizumab positron emission tomography for imaging angiogenesis in patients with inflammatory breast carcinoma receiving preoperative chemotherapy
Authors: HA Jacene, B Overmoyer, EJ Schlosnagle, A Abbott, E Yeh, J Paolino, S Goel, A Culhane, JR Bellon, F Nakhlis, J Hirshfield-Bartek, A Van den Abbeele
Journal: Cancer Research (2017)

Abstract Background: Inflammatory breast cancer (IBC) continues to have a poor prognosis despite standard tri-modality treatment with chemotherapy, mastectomy and radiation. Current methods of assessing primary tumor response (i.e., clinical exam and breast magnetic resonance imaging [MRI]) are limited for distinguishing residual tumor from responsive disease because of persistent morphologic changes in the breast. Therefore, the inability to accurately assess tumor response during treatment often results in the continuation of ineffective systemic chemotherapy until definitive pathologic evaluation at mastectomy. IBC has a highly angiogenic phenotype which is believed to play a role in this tumor's aggressiveness. The novel radiotracer Zirconium-89 (89Zr)-bevacizumab was developed for imaging tumor angiogenesis with PET. We hypothesize that, as an imaging biomarker of angiogenesis, 89Zr-bevacizumab-PET/CT is a more specific noninvasive functional imaging modality for detecting the presence of tumor angiogenesis compared to current diagnostic methods and will serve as a predictor of response to therapy in patients (pts) with IBC. Methods: Pts with newly diagnosed HER2neg IBC who will receive preoperative chemotherapy are eligible for this pilot study. 89Zr-bevacizumab-PET/CT, breast MRI and FDG-PET/CT are performed before, after 2 cycles, and at the completion of preoperative therapy. Biopsies of primary IBC tumors are obtained prior to and after 2 cycles of preoperative therapy. At the completion of preoperative therapy, pts proceed to mastectomy or biopsy if ineligible to proceed to mastectomy based on current standards for assessing primary tumor response, i.e., clinical exam, breast MRI and lack of systemic progression. At the time of mastectomy, standard evaluation of the surgical specimen will determine pathologic response of IBC to preoperative chemotherapy. A research sample will be collected if residual cancer is present at the time of mastectomy for histologic evaluation of tumor angiogenesis. Objectives/Correlatives: The primary objective is to determine feasibility of 89Zr-bevacizumab-PET/CT imaging in pts with IBC. The primary endpoint is assessment of radiolabeling of chelated bevacizumab and number of successfully acquired 89Zr-bevacizumab-PET/CT scans. Correlative studies will be performed on IBC tissue to assess extent of angiogenesis including microvessel density, vessel diameter, vascular pericyte coverage and tumor VEGF levels. Secondary objectives are: 1) To determine if 89Zr-bevacizumab accumulation in primary IBC tumors correlates with the extent of angiogenesis determined by correlative analysis on IBC tissue; 2) To assess the predictive value of 89Zr-bevacizumab-PET/CT after 2 cycles and at the end of preoperative therapy for determining pathologic response at mastectomy as given by residual cancer burden. Statistics: This is an accrual, not statistical based, feasibility justification. Planned sample size is 10 in order to make a preliminary statement about feasibility and ability for 89Zr-bevacizumab-PET/CT to serve as a surrogate in vivo biomarker of tumor angiogenesis and response to preoperative chemotherapy. Clinical Trial Information: NCT01894451. Citation Format: Jacene HA, Overmoyer B, Schlosnagle EJ, Abbott A, Yeh E, Paolino J, Goel S, Culhane A, Bellon JR, Nakhlis F, Hirshfield-Bartek J, Van den Abbeele A. Pilot study of zirconium-89 bevacizumab positron emission tomography for imaging angiogenesis in patients with inflammatory breast carcinoma receiving preoperative chemotherapy [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 OT2-02-03.