Abstract OT1-17-01: Protocol Description of Genetics and Inflammatory Markers to predict Chemotherapy-Induced Peripheral Neuropathy among Early Stage Breast Cancer Patients Receiving Taxane Therapy – GENIE Study
Authors: Wei Mei , Sharma Anukriti , Johnson Ken , Bie Bihua , hershberger courtney , Sen Alper , Rhoades Emily E. , Hocking Chi-Fan , Budd George , Henry N. Lynn , Eng Charis , Foss Joseph , rotroff daniel 
Published: March 2023

Abstract
Background Chemotherapy induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects seen among patients with early stage breast cancer and received taxane-containing regimens. The primary clinical manifestation of CIPN is sensory neuropathy such as numbness, tingling and pain in hands and feet, which negatively affect the patient’s quality of life (QoL). Although in most patients, CIPN improves over time, in a subset of patients, it remains a substantial debilitating problem, significantly affecting QoL. To date, there are no effective prevention strategies- or sufficient treatment due to the limited understanding of CIPN pre-disposing factors or pathophysiology. We hypothesize that a multimodal integration of biomarkers with CIPN progression analysis will be required to understand the pathophysiology and to consistently predict patient susceptibility. Further, we hypothesize that this multimodal approach may be leveraged to identify targets for CIPN treatment and/or prevention. This abstract describes the study protocol used to explore this hypothesis. Objective This study is designed to 1) identify genetic, transcriptional, epigenetic, metabolic, inflammatory biomarkers predictive of CIPN development among patients with early stage breast cancer receiving a taxane containing therapy; 2) With these biomarkers, develop an algorithm to identify patients who are at risk of developing CIPN before or during taxane therapy. Methods This is a longitudinal, multicenter, observational study. Patients with early-stage breast cancer who are receiving a taxane-containing (paclitaxel, docetaxel or nab-paclitaxel) treatment regimen, without preexisting peripheral neuropathy are eligible. Estimated enrollment is 400 patients. Demographic and clinical data are collected after patients consent to participate. Molecular data and patient reported outcomes (PRO) are collected prior to initiation of taxane therapy, the 4th, 8th, and 12th week of taxane therapy, and at 3, 6, and 9 months after completion of taxane therapy. Blood samples are collected for molecular data which include genetic, transcriptional, epigenetic (DNA-methylation), and metabolic data. PRO are assessed using (i) the European Organization for Research and Treatment of Cancer CIPN20 questionnaire, (ii) the Brief Pain Inventory, (iii) the Pain Catastrophizing Scale, and (iv) the PRO Measurement System for anxiety, depression and pain interference. Initial data analysis will characterize the association of biomarkers in each modality (e.g., genetic, epigenetic, etc.) with the presence or absence of CIPN, and machine learning will be used to build candidate biomarker signatures to predict CIPN before and during taxane treatment. Two distinct multi-modal prediction models will be constructed: 1) a pre-treatment model to predict risk of developing CIPN, and 2) an on-treatment model to predict the onset of CIPN. The goal is to develop a parsimonious, clinically translatable model for robust and accurate predictions of taxane-induced CIPN. Trial Status: Active, 135 subjects enrolled. Trial Centers: 1) Cleveland Clinic Foundation (8 regional sites in Ohio and 1 in Florida); 2) Huntsman Cancer Institute, University of Utah Research Funding: National Institute of Neurological Disorder and Stroke. Grant No.: 1R61NS113258-01A1
Citation Format: Mei Wei, Anukriti Sharma, Ken Johnson, Bihua Bie, courtney hershberger, Alper Sen, Emily E. Rhoades, Chi-Fan Hocking, George Budd, N. Lynn Henry, Charis Eng, Joseph Foss, daniel rotroff. Protocol Description of Genetics and Inflammatory Markers to predict Chemotherapy-Induced Peripheral Neuropathy among Early Stage Breast Cancer Patients Receiving Taxane Therapy – GENIE Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-17-01.