Multidimensional Molecular Profiling Of Repeated Metastatic Tnbc Biopsies In The Intensive Trial Of Omics < Itomic > Safely Guides Treatment Decisions

Background Metastatic triple negative breast cancer (mTNBC) is an inherently diverse disease and while molecular classification of mTNBC has assisted in treatment decisions, if based on only an initial biopsy, it does not take into account the evolution of metastatic cancer. Characterization of emerging metastases is needed to reveal both new resistance or sensitivity to available therapeutics. The goal of “Intensive Trial of OMics in Cancer (ITOMIC) - Intensive Longitudinal Monitoring in Subjects With Triple-Negative Breast Cancer” (NCT01957514) - was to determine the feasibility of longitudinal collection of patient biopsies that would be subjected to molecular analysis to provide actionable, relevant and timely information to guide treatment decisions.Methods Multiple biopsies were collected longitudinally, including pre- and post-treatment, from 29 mTNBC patients enrolled in the ITOMIC study and subjected to multi-dimensional molecular profiling including WES, WGS, cancer gene panel sequencing, RNA-seq, and proteomics and/or IHC for tumor biomarkers. This information was used to guide iterative, patient- and tumor- individualized treatment recommendations made by a multi-institutional ITOMIC Tumor Board (ITB) and conveyed to each subject’s oncologist.Results Longitudinal biopsy collection was found to be safe. Molecular profiling revealed that 2 of an original 31 enrolled subjects likely had lung cancer rather than mTNBC, supporting the merit of repeated tissue analysis. While the other 29 subjects had all been given a diagnosis of mTNBC before entering the trial, estrogen receptor, progesterone receptor, and/or HER2 were found to be over-expressed in at least one sample for 12 subjects; appearance of receptor positivity suggests targeted therapy may be effective. Tumor evolution in response to the first on-study treatment for most subjects (cisplatin) was revealed by copy number alterations, changes in single nucleotide variants, and insertions/deletions in pre-/post-treatment biopsies. Over the course of the study, the ITB convened 54 times and 39 of 182 recommended treatments were evaluated and accessed through either an existing clinical trial, a single patient IND, approved off label or label indication. While not all ITB treatment recommendations were followed, 24 subjects did receive at least one ITB-recommended drug, frequently as part of a clinical trial. Currently, for 27 subjects (2 withdrew) median survival is ~31 months. There are 4 surviving patients in treatment with a remarkable median survival of \u003e51 months.Conclusion Collection and molecular analysis of multiple biopsies during the course of patient’s disease, shown here to be safe and feasible, provides information vital to appropriate treatment choice and reveals new targets for and resistance to therapy in metastatic TNBC. Citation Format: Kimberly A Burton, Eric Q Konnick, Sibel Blau, Michael O Dorschner, Julie Gralow, Rahul Parulkar, Elisabeth Mahen, Patricia Spilman, Stephanie Parker, Francis M Senecal, Colin Pritchard, Christopher Szeto, Jing Zhu, Vijayakrishna K Gadi, Stephen C Benz, Shahrooz Rabizadeh, Patrick Soon-Shiong, Carl Anthony Blau. Multidimensional molecular profiling of repeated metastatic TNBC biopsies in the intensive trial of omics lITOMICg safely guides treatment decisions [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-13.