Felix C Saalfeld1, Carina Wenzel2, Petros Christopoulos3, Sabine Merkelbach-Bruse4, Timm M Reissig5, Silke Laßmann6, Sebastian Thiel7, Jan A Stratmann8, Ralf Marienfeld9, Johannes Berger10, Alexander Desuki11, Janna-Lisa Velthaus12, Diego Kauffmann-Guerrero13, Albrecht Stenzinger14, Sebastian Michels15, Thomas Herold16, Michael Kramer1, Sylvia Herold2, Amanda Tufman13, Sonja Loges17, Jürgen Alt11, Maria Joosten18, Gerlinde Schmidtke-Schrezenmeier19, Martin Sebastian8, Susann Stephan-Falkenau20, Cornelius F Waller21, Marcel Wiesweg5, Jürgen Wolf15, Michael Thomas3, Daniela E Aust2, Martin Wermke22. 1. Clinic for Internal Medicine I, University Hospital, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. 2. Department for Pathology, University Hospital, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. 3. Thoraxklinik at University Hospital, Röntgenstraße 1, 69126 Heidelberg, Germany; Translational Lung Research Center Heidelberg, member of the German Center for Lung Research (DZL). 4. Institute of Pathology, University Hospital, University of Cologne, Kerpener Straße 62, 50937 Köln, Germany. 5. West German Cancer Center, Department of Medical Oncology, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. 6. Institute for Surgical Pathology, University Medical Centre Freiburg and Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany. 7. Department of Pneumology, Helios Clinic Emil von Behring, Walterhöferstr. 11, 14165 Berlin, Germany. 8. Department of Medicine, Hematology/Oncology, University Hospital, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. 9. Institute of Pathology, University Hospital, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. 10. Charité Comprehensive Cancer Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany. 11. UCT Mainz und 3rd. Med. Department, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. 12. Department of Oncology, Hematology and Bone Marrow Transplantation with section Pneumology, Hubertus Wald University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20251 Hamburg, Germany. 13. Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology Center Munich, University of Munich (LMU), Marchioninistraße 15, 81377 Munich, Germany. 14. Translational Lung Research Center Heidelberg, member of the German Center for Lung Research (DZL); Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg. 15. Clinic I for Internal Medicine, University Hospital, University of Cologne, Kerpener Straße 62, 50937 Köln, Germany. 16. Department of Pathology, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. 17. Department of Oncology, Hematology and Bone Marrow Transplantation with section Pneumology, Hubertus Wald University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20251 Hamburg, Germany; Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 224, 69120 Heidelberg, Germany; Department of Personalized Oncology, University Hospital Mannheim, Mannheim, Germany. 18. Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany. 19. Department of Internal Medicine II, University Medical Center Ulm, 89070 Ulm, Germany. 20. Department of Pathology, Helios Klinikum Emil von Behring, Walterhöferstr. 11, 14165 Berlin, Germany. 21. Department of Haematology, Oncology and Stem Cell Transplantation, University Medical Centre Freiburg and Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany. 22. Clinic for Internal Medicine I, University Hospital, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Electronic address: martin.wermke@uniklinikum-dresden.de.
Abstract
INTRODUCTION: In contrast to other driver mutations, no targeted therapies have yet been approved in ERBB2 mutated non-small cell lung cancer (HER2mu NSCLC). However, several compounds have shown promising early efficacy data, which need to be evaluated in the context of current standard approaches. While data on the efficacy of immune checkpoint inhibitors (ICI) in second or later lines of treatment remain limited and conflicting, there are virtually no data on patient outcome under ICI / platinum doublet combinations in the first-line setting. METHODS: We retrospectively assessed outcomes of HER2mu NSCLC patients treated with ICI alone or in combination with chemotherapy within the German nNGM consortium by means of overall response rate (ORR), progression-free, and overall survival (PFS and OS). RESULTS: ICI either in combination with chemotherapy or as monotherapy were applied as first-line treatment in 27 patients, whereas 34 received single agent ICI in second or later lines. Patient characteristics were in line with previously published data. In treatment-naïve patients receiving ICI in combination with chemotherapy the ORR, median PFS, and OS rate at 1 year were 52%, 6 months, and 88%, respectively. In second or later lines ICI monotherapy was associated with an ORR of 16%, a median PFS of 4 months, and a median OS of 10 months. CONCLUSIONS: Immune checkpoint inhibitors are effective as monotherapy and in combination with platinum doublet chemotherapy. Therefore, ICI based treatments may be seen as the current standard of care and benchmark for targeted therapies in HER2mu NSCLC.
INTRODUCTION: In contrast to other driver mutations, no targeted therapies have yet been approved in ERBB2 mutated non-small cell lung cancer (HER2mu NSCLC). However, several compounds have shown promising early efficacy data, which need to be evaluated in the context of current standard approaches. While data on the efficacy of immune checkpoint inhibitors (ICI) in second or later lines of treatment remain limited and conflicting, there are virtually no data on patient outcome under ICI / platinum doublet combinations in the first-line setting. METHODS: We retrospectively assessed outcomes of HER2mu NSCLCpatients treated with ICI alone or in combination with chemotherapy within the German nNGM consortium by means of overall response rate (ORR), progression-free, and overall survival (PFS and OS). RESULTS: ICI either in combination with chemotherapy or as monotherapy were applied as first-line treatment in 27 patients, whereas 34 received single agent ICI in second or later lines. Patient characteristics were in line with previously published data. In treatment-naïve patients receiving ICI in combination with chemotherapy the ORR, median PFS, and OS rate at 1 year were 52%, 6 months, and 88%, respectively. In second or later lines ICI monotherapy was associated with an ORR of 16%, a median PFS of 4 months, and a median OS of 10 months. CONCLUSIONS: Immune checkpoint inhibitors are effective as monotherapy and in combination with platinum doublet chemotherapy. Therefore, ICI based treatments may be seen as the current standard of care and benchmark for targeted therapies in HER2mu NSCLC.