Abstract OT3-2-01: IMPACT: IMaging PAtients for Cancer drug selecTion – Metastatic breast cancer (MBC)
Authors: Bensch Frederike , Brouwers Adrienne , Glaudemans Andor , de Jong Johan , de Vries Erik , van de Graaf Winette , Boon Eline , Oyen Wim , de Geus-Oei Lioe-Fee , Visser Eric , van Helden Erik , Menke-van der Hoeven van Oordt Willemien , Verheul Henk , Hoekstra Otto , Janssen Jim , Huisman Marc , Elias Sjoerd , Moons Carl , de Vries Liesbeth , Schröder Carolien 
Published: May 2015

Abstract
Background: Therapy of newly identified MBC is largely based on estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. Optimal receptor information should be up-to-date and preferably from the whole body, given receptor conversion over time and intra-patient tumor heterogeneity. Novel molecular imaging by means of 18F-fluoroestradiol (FES)- and 89Zr-trastuzumab-PET/CT is a non-invasive, patient friendly way to obtain such information. Comprehensive prospective data comparing novel molecular imaging, metastasis biopsy and blood biomarkers, are needed to assess clinical utility for optimal therapy guidance and response prediction.
Trial design: The IMPACT-MBC trial (NCT01957332), is a multicenter prospective cohort study, supported by the Dutch Cancer Society-Alpe d’HuZes, in which n=200 newly diagnosed MBC patients will be entered. Prior to start of treatment patients will undergo i) standard MBC work up including bone scan, diagnostic CT and 18F-fluorodeoxyglucose(FDG)-PET/CT, ii) a metastasis biopsy, for standard (immuno)pathology and DNA sequencing, iii) 18F-FES- and 89Zr-trastuzumab-PET/CT to assess whole-body metastatic ER and HER2 status, and iv) blood sampling (CTCs, ctDNA, germline DNA, 89Zr-radioactivity measurements). Treatment advice will be based on standard work up and experimental PET scans. Tumor response is assessed by a 2 week 18F-FDG-PET/CT (experimental) and an 8 week diagnostic CT (standard; primary outcome).
Eligibility criteria: All newly diagnosed non-rapidly progressive MBC patients with measurable or clinical evaluable (bone only) disease can be enrolled, regardless of primary tumor ER and HER2 status. Patients should be eligible for systemic therapy, but not require immediate start of chemotherapy. A histological biopsy of a metastatic lesion should be safely obtainable. Excluded are pregnant or lactating women and patients with a prior allergic reaction to immunoglobulins.
Specific aims: i) To assess the (added) clinical utility of 18F-FES- and 89Zr-trastuzumab-PET/CT, in the setting of MBC at first presentation, in relation to other diagnostics, ii) to assess the relation of experimental 18F-FES-, 89Zr-trastuzumab- and 2 week 18F-FDG-PET/CT with (progression free) survival and iii) to assess the cost-effectiveness of the experimental PET/CT scans.
Statistical methods: IMPACT-MBC aims to model the predictive value of several tests (novel molecular imaging, biopsy and blood biomarkers) in combination, by means of multivariable regression-model based techniques, combined with state-of-the-art methods for estimating the added value of novel tests to existing information (e.g. NRI, IDI). All these analyses will be employed both on (predicting responsiveness on) a patient- and metastasis level.
Present accrual and target accrual: The IMPACT-MBC trial was opened for accrual at the University Medical Center (UMC) Groningen, in August 2013. Accrual rate is as anticipated 2-3 patients/month/center. The two other participating centers, Radboud MC Nijmegen and VUmc Amsterdam recently opened. It is anticipated that accrual of patients will be finalized in 2016.
Citation Format: Frederike Bensch, Adrienne Brouwers, Andor Glaudemans, Johan de Jong, Erik de Vries, Winette van de Graaf, Eline Boon, Wim Oyen, Lioe-Fee de Geus-Oei, Eric Visser, Erik van Helden, Willemien Menke-van der Hoeven van Oordt, Henk Verheul, Otto Hoekstra, Jim Janssen, Marc Huisman, Sjoerd Elias, Carl Moons, Liesbeth de Vries, Carolien Schröder. IMPACT: IMaging PAtients for Cancer drug selecTion – Metastatic breast cancer (MBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-2-01.