Download PDF
Urologie Scan 2016; 03(01): 57-70
DOI: 10.1055/s-0042-100944
Fortbildung
Uroonkologie
© Georg Thieme Verlag KG Stuttgart · New York

Immunonkologie bei urologischen Tumoren

Axel S. Merseburger
,
Marie C. Hupe
,
Mario W. Kramer
Further Information

Publication History

Publication Date:
17 March 2016 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die Erforschung der Interaktion zwischen Tumor und Immunsystem hat in der letzten Zeit zu Zulassungen neuer Substanzen geführt, die durch Blockade von Immunantwort-Checkpoints ein Entweichen der Tumorzelle vor dem Immunsystem verhindern. Zu diesen sogenannten Checkpoint-Inhibitoren gehören CTLA-4- (Cytotoxic T-Lymphocyte-associated Antigen 4), PD-1 (Programmed Cell Death 1) und PD-L1-Inhibitoren (PD-L1: Programmed Cell Death Ligand 1). Die Substanzen sind gegenwärtig Gegenstand einer Vielzahl klinischer Studien. Im Bereich der Urologie sind die Studien beim Nierenzellkarzinom und Urothelkarzinom am weitesten fortgeschritten. In den aktuellen EAU-Empfehlungen ist der Checkpoint-Inhibitor Nivolumab sogar bereits eine mögliche Zweitlinienoption beim metastasierten Nierenzellkarzinom. Aufgrund des neuen immunmodulierenden Therapieansatzes sind Besonderheiten beim Therapiemonitoring hinsichtlich Nebenwirkungen und Ansprechkriterien zu beachten.

 

  • Literatur

  • 1 Hodi FS, OʼDay SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723
    CrossrefSearch in Google Scholar
  • 2 Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol 2015; 33: 1974-1982
    CrossrefSearch in Google Scholar
  • 3 Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 252-264
    CrossrefSearch in Google Scholar
  • 4 Herbst RS, Baas P, Kim DW et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 18.12.2015; pii: S0140-6736(15)01281-7.
    Search in Google Scholar
  • 5 Drake CG, McDermott DF, Sznol M et al. Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up. J Clin Oncol 2013; 31 (Suppl.): Abstract 4514
    Search in Google Scholar
  • 6 Motzer RJ, Rini BI, McDermott DF et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol 2015; 33: 1430-1437
    CrossrefSearch in Google Scholar
  • 7 Motzer RJ, Escudier B, McDermott DF et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; 373: 1803-1813
    CrossrefSearch in Google Scholar
  • 8 Goebell PJ, Bedke J. Molekulare Konzepte der Immunmodulation zur Behandlung des metastasierten Nierenzellkarzinoms: Wo stehen wir?. Aktuelle Urol 2015; 46: 473-480
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Yang JC, Hughes M, Kammula U et al. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother 2007; 30: 825-830
    CrossrefSearch in Google Scholar
  • 10 Hammers HJ, Plimack ER, Infante JR et al. Expanded cohort results from CheckMate 016: A phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). J Clin Oncol 2015; 33 (Suppl.): Abstract 4516
    Search in Google Scholar
  • 11 Hammers HJ, Plimack ER, Sternberg C et al. CheckMate 214: A phase III, randomized, open-label study of nivolumab combined with ipilimumab versus sunitinib monotherapy in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 2015; 33 (Suppl.): Abstract TPS4578
    Search in Google Scholar
  • 12 Rosenberg JE. Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 210). ESMO@ECC. 2015 Abstract 21LBA
    Search in Google Scholar
  • 13 Miyahira AK, Kissick HT, Bishop JL et al. Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden prostate cancer academy meeting. Prostate 2015; 75: 337-347
    CrossrefSearch in Google Scholar
  • 14 Small EJ, Schellhammer PF, Higano CS et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006; 24: 3089-3094
    CrossrefSearch in Google Scholar
  • 15 Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411-422
    CrossrefPubMedSearch in Google Scholar
  • 16 Small EJ, Tchekmedyian NS, Rini BI et al. A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin Cancer Res 2007; 13: 1810-1815
    CrossrefSearch in Google Scholar
  • 17 van den Eertwegh AJ, Versluis J, van den Berg HP et al. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol 2012; 13: 509-517
    CrossrefSearch in Google Scholar
  • 18 Kwon ED, Drake CG, Scher HI et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2014; 15: 700-712
    CrossrefSearch in Google Scholar
  • 19 Topalian SL, Hodi FS, Brahmer JR et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366: 2443-2454
    CrossrefSearch in Google Scholar
  • 20 Albers P, Albrecht W, Algaba F et al. Guidelines on Testicular Cancer: 2015 Update. Eur Urol 2015; 68: 1054-1068
    CrossrefPubMedSearch in Google Scholar
  • 21 Cierna Z, Mego M, Miskovska V et al. Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors. Ann Oncol 2016; 27: 300-305
    CrossrefSearch in Google Scholar
  • 22 Cheng X, Dai H, Wan N et al. Interaction of programmed death-1 and programmed death-1 ligand-1 contributes to testicular immune privilege. Transplantation 2009; 87: 1778-1786
    CrossrefSearch in Google Scholar
  • 23 Fankhauser CD, Curioni-Fontecedro A, Allmann V et al. Frequent PD-L1 expression in testicular germ cell tumors. Br J Cancer 2015; 113: 411-413
    CrossrefSearch in Google Scholar
  • 24 Bernard BD, Albiges L, Signoretti S et al. Programmed death-ligand 1 (PD-L1) expression in cured and not cured testicular and other germ cell tumors (GCT). J Clin Oncol 2016; 34 (Suppl. 02) 485 Abstract
    CrossrefSearch in Google Scholar
  • 25 A Phase II Single-Arm Multi-Center Trial Evaluating the Efficacy of Pembrolizumab in the Treatment of Subjects with Incurable Platinum-Refractory Germ Cell Tumors: Hoosier Cancer Research Network GU14-206. https://clinicaltrials.gov/ct2/show/NCT02499952?term=NCT02499952&rank=1
  • 26 Wang J, Rodriguez J, Rao P et al. Programmed death ligand-1 (PD-L1) expression in penile squamous cell carcinoma. J Clin Oncol 2015; 33 (Suppl. 07) 393 Abstract
    Search in Google Scholar
  • 27 Wolchok JD, Hoos A, O'Day S et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15: 7412-7420
    CrossrefSearch in Google Scholar
  • 28 Ribas A, Chmielowski B, Glaspy JA. Do we need a different set of response assessment criteria for tumor immunotherapy?. Clin Cancer Res 2009; 15: 7116-7118
    CrossrefSearch in Google Scholar
  • 29 Powles T, Staehler M, Ljungberg B et al. Updated EAU guidelines for clear cell renal cancer patients who fail VEGF targeted therapy. Eur Urol 2016; 69: 4-6
    CrossrefSearch in Google Scholar