title: Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: 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.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Zschäbitz
authors.affiliation: Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany. Electronic address: Felix.Lasitschka@med.uni-heidelberg.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.affiliation: Department of Urology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Electronic address: Boris.Hadaschik@med.uni-heidelberg.de.
authors.forename: Boris
authors.initials: B
authors.lastname: Hadaschik
authors.affiliation: Interdisciplinary Tumor Center, Mannheim University Hospital, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany. Electronic address: Ralf-Dieter.Hofheinz@medma.uni-heidelberg.de.
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hofheinz
authors.affiliation: Private Practice, Hasselbachplatz 2, 39104 Magdeburg, Germany. Electronic address: ju@onkologie-magdeburg.de.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Jentsch-Ullrich
authors.affiliation: Private Practice, Mooslohstraße 53, 92637 Weiden in der Oberpfalz, Germany. Electronic address: info@hejazi-gruener.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Grüner
authors.affiliation: 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.
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.affiliation: 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.
authors.forename: Carsten
authors.initials: C
authors.lastname: Grüllich
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D031954:Choriocarcinoma, Non-gestational / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D002945:Cisplatin / Q000627:therapeutic use; D057176:Compassionate Use Trials; D018240:Endodermal Sinus Tumor / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009373:Neoplasms, Germ Cell and Embryonal / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000077594:Nivolumab; D017671:Platinum Compounds / Q000008:administration & dosage; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012189:Retrospective Studies; D018239:Seminoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D033581:Stem Cell Transplantation; D013724:Teratoma; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014057:Tomography, X-Ray Computed; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C105992:PDCD1 protein, human; D017671:Platinum Compounds; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; D005047:Etoposide; C582435:pembrolizumab; D002945:Cisplatin; D007069:Ifosfamide
keywords: Checkpoint inhibition; Germ cell cancer; Immunotherapy; PD-1; PD-L1; Platinum refractory disease; Testicular cancer