Abstract 3165: An evidence-based software tool for personalized cancer medicine to recommend therapeutic options and avoid toxicity
Authors: Matthias Löhr, Katrin Stecker, Caroline Huelsewig, Sandra Morandell, Isin Ertongur, Sarah Luke-Glaser, Anna Laib, Linnéa Malgerud, Carlos Fernández Moro, Masoud Karimi, Johan Permert, Rainer Heuchel, Johan Lindberg, Valtteri Wirta, Alexander Picker, Marco Del Chiaro, Stephan L. Haas, Caroline S. Verbek, Lars Engstrand, Jens Siveke, David Jackson, Henrik Grönberg, Dirk Jäger, Stephan Brock
Journal: Cancer Research (2016)

Abstract Background. For many tumors, therapeutic options are sparse beyond the guidelines, especially for pancreatic cancer. At the same time, more and more biomarkers are known, informing about or supporting treatment decisions. Finally, tumor DNA analysis with next generation sequencing (NGS) is quickly becoming a routine test, at least for tumors. However, to analyse the vast amount of data and provide concrete, evidence-based treatment recommendations has been a challenge. Methods. Applying NGS in a quality controlled set-up together with the newly developed evidence-based software tool EngineusGUIDETM (CE-marked). Results. During the time from Oct 2013 until Oct 2015, 87 patients were analysed with EngineusGUIDE. In 7 cases, more than one tumor was investigated. NGS was performed (WXS = 48; panel/paired = 16, panel = 23). Sequencing could be performed in all but one patient (Whole Exome; bone metastasis). Sequencing quality was insufficient for analysis in 3 cases (paired panel), sequencing revealed insufficient tumor content in the sample for one patient (Whole Exome) leaving 82 patients. The indication was: Pancreatic Neoplasms = 21 cases; Colorectal Neoplasms = 12; Breast Neoplasms = 5; CUP = 6; NSCLC = 3; 2 cases each for Bronchial Neoplasms, Adenoid Cystic Carcinoma, Common Bile Duct Neoplasms, Glioblastoma, Multiple Myeloma, Prostatic Neoplasms and 1 case each for Adenocarcinoma, Duodenal Neoplasms, Endometrial Neoplasms, Hemangiosarcoma, Hypopharyngeal Neoplasms, Leukemia (Lymphocytic, Chronic, B-Cell), Liposarcoma, Liver Neoplasms, Lung Neoplasms, B-Cell Lymphoma, Mantle-Cell Lymphoma, Meningioma, Oropharyngeal Neoplasms, Ovarian Neoplasms, Paranasal Sinus Neoplasms, Parathyroid Neoplasms, Sarcoma, Sigmoid Neoplasms, Squamous Cell Neoplasms, Stomach Neoplasms, Thyroid Neoplasms, Urinary Bladder Neoplasms, Uveal melanoma. In 67/82 patients, druggable targets (response biomarkers) could be identified (range 0-8; median 2). In 45/82 patients (range 0-5; median 1) biomarkers indicated lack of efficacy (e.g. KRAS mutation in CRC). In 65/82 patients, biomarkers indicated increased toxicity (range 0-7; median 2), in 19/82 patients FDA-approved biomarkers for toxicity were detected (28 biomarkers). Of the positive biomarkers, 40 biomarkers in 26 patients indicated drugs approved in the indication, 75 biomarkers in 45 patients indicated approved drugs, and 58 biomarkers in 39 patients indicated experimental drugs (pre-clinical and phase I - III). Six patients have already received drugs recommended by EngineusGUIDE. In 11 patients, toxicity markers may explain observed toxicity during previous treatment. We are currently collecting the outcome parameters of EngineusGUIDE recommendations. Citation Format: Matthias Löhr, Katrin Stecker, Caroline Huelsewig, Sandra Morandell, Isin Ertongur, Sarah Luke-Glaser, Anna Laib, Linnéa Malgerud, Carlos Fernández Moro, Masoud Karimi, Johan Permert, Rainer Heuchel, Johan Lindberg, Valtteri Wirta, Alexander Picker, Marco Del Chiaro, Stephan L. Haas, Caroline S. Verbek, Lars Engstrand, Jens Siveke, David Jackson, Henrik Grönberg, Dirk Jäger, Stephan Brock. An evidence-based software tool for personalized cancer medicine to recommend therapeutic options and avoid toxicity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3165.