Stefanie Zschäbitz1, Felix Lasitschka2, Boris Hadaschik3, Ralf-Dieter Hofheinz4, Kathleen Jentsch-Ullrich5, Marcus Grüner6, Dirk Jäger7, Carsten Grüllich8. 1. Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. Electronic address: Stefanie.Zschaebitz@med.uni-heidelberg.de. 2. Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany. Electronic address: Felix.Lasitschka@med.uni-heidelberg.de. 3. Department of Urology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Electronic address: Boris.Hadaschik@med.uni-heidelberg.de. 4. Interdisciplinary Tumor Center, Mannheim University Hospital, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany. Electronic address: Ralf-Dieter.Hofheinz@medma.uni-heidelberg.de. 5. Private Practice, Hasselbachplatz 2, 39104 Magdeburg, Germany. Electronic address: ju@onkologie-magdeburg.de. 6. Private Practice, Mooslohstraße 53, 92637 Weiden in der Oberpfalz, Germany. Electronic address: info@hejazi-gruener.de. 7. Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. Electronic address: Dirk.Jaeger@med.uni-heidelberg.de. 8. Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. Electronic address: Carsten.Gruellich@med.uni-heidelberg.de.
Abstract
INTRODUCTION: Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. PATIENTS AND METHODS: We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. RESULTS: Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. INTERPRETATION: We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted.
INTRODUCTION: Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. PATIENTS AND METHODS: We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. RESULTS: Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. INTERPRETATION: We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted.
Authors: M Mego; D Svetlovska; M Chovanec; M Rečkova; K Rejlekova; J Obertova; P Palacka; Z Sycova-Mila; U De Giorgi; J Mardiak Journal: Invest New Drugs Date: 2019-06-01 Impact factor: 3.850
Authors: Jiaqi Zhang; Yeye Chen; Lei Liu; Mengxin Zhou; Cheng Huang; Chao Guo; Shanqing Li Journal: Cancer Manag Res Date: 2021-11-13 Impact factor: 3.989
Authors: Michal Chovanec; Zuzana Cierna; Viera Miskovska; Katarina Machalekova; Katarina Kalavska; Katarina Rejlekova; Daniela Svetlovska; Dusan Macak; Stanislav Spanik; Karol Kajo; Pavel Babal; Ugo De Giorgi; Michal Mego; Jozef Mardiak Journal: Br J Cancer Date: 2018-02-27 Impact factor: 7.640