Results of the extended analysis for cancer treatment (EXACT) trial: a prospective translational study evaluating individualized treatment regimens in oncology

// Gerald W. Prager 1, 8 , Matthias Unseld 1, 8 , Fredrik Waneck 3, 8 , Robert Mader 1, 8 , Fritz Wrba 2, 8 , Markus Raderer 1, 8 , Thorsten Fuereder 1, 8 , Phillip Staber 4, 8 , Ulrich Jager 4, 8 , Markus Kieler 1, 8 , Daniela Bianconi 1, 8 , Mir Alireza Hoda 7, 8 , Lukas Baumann 9 , Alexander Reinthaller 5, 8 , Walter Berger 6, 8 , Christoph Grimm 5, 8 , Heinz Kolbl 5, 8 , Maria Sibilia 6, 8 , Leonhard Mullauer 2, 8 and Christoph Zielinski 1, 8 1 Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria 2 Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria 3 Department of Interventional Radiology, Medical University of Vienna, Vienna, Austria 4 Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria 5 Department of General Gynecology and Gynecological Oncology, Medical University of Vienna, Vienna, Austria 6 Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria 7 Department of Surgery, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria 8 Comprehensive Cancer Center of the Medical University of Vienna, Vienna, Austria 9 Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria Correspondence to: Gerald W. Prager, email: gerald.prager@meduniwien.ac.at Keywords: precision medicine; molecular profile Received: May 28, 2018 Accepted: January 02, 2019 Published: January 29, 2019 ABSTRACT Background: The concept of personalized medicine defines a promising approach in cancer care. High-throughput genomic profiling of tumor specimens allows the identification of actionable mutations that potentially lead to tailored treatment for individuals’ benefit. The aim of this study was to prove efficacy of a personalized treatment option in solid tumor patients after failure of standard treatment concepts. Results: Final analysis demonstrates that 34 patients (62%) had a longer PFS upon experimental treatment (PFS1) when compared to previous therapy (PFS0); PFS ratio > 1.0 ( p = 0.002). The median PFS under targeted therapy based on molecular profiling (PFS1) was 112 days (quartiles 66/201) and PFS0 = 61 days (quartiles 51/92; p = 0.002). Of the 55 patients, 31 (56%) showed disease control (DCR), consisting of 2 (4%) patients which achieved a complete remission, 14 (25%) patients with a partial remission and 15 (27%) patients who had a stabilization of disease. Median OS from start of experimental therapy was 348 days (quartiles 177/664). Conclusion: The prospective trial EXACT suggests that treatment based on real-time molecular tumor profiling leads to superior clinical benefit. Materials and Methods: In this prospective clinical phase II trial, 55 cancer patients, after failure of standard treatment options, aimed to achieve a longer progression-free survival on the experimental treatment based on the individual’s molecular profile (PFS1) when compared to the last treatment given before (PFS0). The personalized medicine approach was conceived to be clinical beneficial for patients who show a PFS ratio (PFS 1/PFS0) of > 1.0.