Title of Presentation
Use of Biomarkers to Guide Clinical Decisions in the Context of Precision Medicine
Date and Place
Christian Dittrich, Professor of Medicine at the Vienna University School of Medicine, is head of the 3rd Medical Department – Centre for Oncology and Haematology at the Kaiser Franz Josef-Spital in Vienna and president of Applied Cancer Research – Institution for Translational Research Vienna (ACR-ITR VIEnna). He served as member on the European Organisation for Research and Treatment of Cancer (EORTC) Protocol Review Committee (PRC), the Scientific Audit Committee (SAC), and as chair on the EORTC Preclinical Therapeutic Models Group (PTMG) and the New Drug Advisory Committee (NDAC) and as member on the EORTC Board. Recently, he became chair of the EORTC Translational Research Division (TRD). He was chair of the Fellowship and Award Committee of the European Society for Medical Oncology (ESMO) and ESMO representative in the Board and Council of the FECS, nowadays ECCO, as well as ESMO-national representative of Austria. Recently, he became chair of the ESMO/ASCO Global Curriculum Working Group and coordinator of the ESMO Faculty for Principles of Clinical Trials and Systemic Therapy. Representing ESMO, he was faculty member and co-director of the Clinical Trials Workshops in Flims/Zeist. He has been running a CME-initiative in trials methodology in German language under the patronage of DESO since 1998. He has research interests in clinical trials’ methodology, new drug development and translational research, focused on solid tumours. He has been acting as principal or co-investigator in numerous clinical trials from phase I to phase III.
Biomarker represent the basis of precision medicine in oncology. Their development is bound to that of new anti-tumour agents, is not trivial and has to be started already during the preclinical developmental process of a new substance. After technical validation, biomarker have to be clinically validated, and their clinical utility has to be confirmed. Although the global definition of a characteristic, that has to be objectively measureable and that correlates with the patho-/biology or the pharmacological response to a therapeutic intervention, holds true for all kinds of biomarker they differ as to their distinct characteristic as pharmacokinetic, pharmacodynamic, prognostic, predictive or pharmacogenomic and therewith their use. Depending on the purpose different designs have been created to test new biomarker clinically, such as stratified, enrichment or strategy designs. Non-small cell lung cancer (NSCLC) is a prototype of a tumour entity the subentities of which are nowadays treated completely different based on their genetic characterisation, i.e. in form of biomarker; NSCLC with activating EGFR mutation (mainly del19): gefitinib, erlotinib, afatinib; EGFR T790M: osimertinib; EML4-ALK translocation: crizotinib, ceritinib, alectinib. Enrichment of patients for BRCA 1 or 2 mutation was the decisive step in the development of the PARP inhibitor olaparib to exert its inhibitory capacity based upon the principle of synthetic lethality in ovarian, breast and prostate cancer. Further successful developments of agents along with biomarker are known from melanoma, thyroid, squamous cell skin, breast or colorectal cancer. Biobanks and their custodians play an important role in the complex process of biomarker development.