TY - JOUR A1 - Hempel, Louisa A1 - Veloso de Oliveira, Julia A1 - Gaumann, Andreas A1 - Milani, Valeria A1 - Schweneker, Katrin A1 - Schenck, Kristina A1 - Fleischmann, Bastian A1 - Philipp, Patrick A1 - Mederle, Stefanie A1 - Garg, Arun A1 - Piehler, Armin A1 - Gandorfer, Beate A1 - Schick, Cordula A1 - Kleespies, Axel A1 - Sellmann, Ludger A1 - Bartels, Marius A1 - Goetze, Thorsten O. A1 - Stein, Alexander A1 - Goekkurt, Eray A1 - Pfitzner, Lucia A1 - Robert, Sebastian A1 - Hempel, Dirk T1 - Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach - A Real World Data Analysis JF - Cancers N2 - After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment. KW - GEJ KW - GC KW - next-generation sequencing KW - Her2neu KW - PD-L1 KW - personalized medicine KW - molecular target KW - checkpoint inhibitors KW - actionable gene variants Y1 - 2021 UR - https://doi.org/10.3390/cancers13174453 VL - 13 IS - 17 SP - 4453 ER - TY - JOUR A1 - Hempel, Louisa A1 - Molnar, Jakob A1 - Gaumann, Andreas A1 - Robert, Sebastian A1 - Scheiber, Josef A1 - Kleespies, Axel A1 - Riedmann, Kristina A1 - Schreiber, Susanne A1 - Gandorfer, Beate A1 - Piehler, Armin A1 - Hempel, Dirk T1 - Detection of acquired resistance mutation ALK G1202R after treatment with alectinib and response of lorlatinib BT - A case report JF - memo - Magazine of European Medical Oncology N2 - In the era of personalized medicine, the identification of driver mutations has paved the way towards targeted therapy. With the identification of anaplastic lymphoma kinase (ALK) as an oncogenic driver mutation, ALK rearrangements became druggable by tyrosine kinase inhibitors and, thus, have improved the prognosis for patients. Nevertheless, these approaches are limited by resistances occurring within the first or second year of administering ALK inhibitors. Among the different ALK resistant mutations, G1202R is the most common mutation, located in the kinase domain of the ALK protein resulting in resistance to treatment with the first- and second-generation kinase inhibitors (e.g., crizotinib, ceritinib, brigatenib and alectinib). Conflicting reports exist regarding the efficacy of lorlatinib, a next generation ALK inhibitor. The aim of this study is to access the potential impact of lorlatinib as a second-line treatment for a metastatic progressive NSCLC disease harboring genomic alteration of ALK G1202R, an AKLi-resistant mutation. The case of a patient with advanced lung cancer and the mentioned mutation is described. KW - NSCLC KW - Next-generation ALK inhibitor KW - Resistance mechanisms KW - Next-generation sequencing KW - Molecular diagnostics Y1 - 2021 UR - https://doi.org/10.1007/s12254-021-00724-2 ER -