Aktuelle Urol 2018; 49(02): 142-156
DOI: 10.1055/s-0043-123067
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Immuntherapie mit Checkpoint-Inhibitoren beim lokal fortgeschrittenen und metastasierten Urothelzellkarzinom

Immunotherapy with checkpoint inhibitors in local advanced and metastatic urothelial carcinoma
Kurt Miller
1   Charite Universitätsmedizin Berlin, Klinik für Urologie
,
Jürgen E. Gschwend
2   Klinikum rechts der Isar der Technischen Universität München
,
Axel Merseburger
3   Universitätsklinikum Schleswig-Holstein, Campus Lübeck
,
Margitta Retz
2   Klinikum rechts der Isar der Technischen Universität München
,
Arnulf Stenzl
4   Universitätsklinik für Urologie, Universitätsklinikum Tübingen
› Author Affiliations
Further Information

Publication History

Publication Date:
27 March 2018 (online)

Zusammenfassung

Checkpoint-Inhibitoren haben in der bislang limitierten Therapie des Urothelzellkarzinoms eine neue Ära eingeleitet. Dies spiegelt sich in der aktuellen S3-Leitlinie zum Harnblasenkarzinom derzeit noch nicht wider. Da es sich bei der Krebsimmuntherapie um ein neues Therapieprinzip handelt, stellen sich gegenwärtig Fragen für den Praxisalltag: Auf welchen Daten beruhen die Zulassungen der einzelnen Wirkstoffe? Wie verändern sich die Therapiealgorithmen? Worauf muss beim Therapiemanagement geachtet werden? Welche Nebenwirkungen können auftreten, wie lassen sie sich erkennen und behandeln? Die vorliegende Publikation verfolgt das Ziel, diese Fragen zu beantworten.

Abstract

The approval of immune checkpoint inhibitors has started a new era in the treatment of urothelial carcinoma, which, so far, has been a disease with limited treatment options. However, in the current German S3 guideline for bladder cancer the remarkable improvements provided by immune checkpoint inhibitors have not been reflected. As cancer immunotherapy is a novel approach, there are several questions related to the daily clinical routine: What clinical data was used as the basis for the approval of the individual substances? What does this mean for previous treatment algorithms? What issues must be considered in the management of adverse events? What side-effects may occur and how can they be recognised and treated? The present paper provides an overview of the new treatment options regarding their relevance as well as recommendations for their application in clinical practice.

 
  • Literatur

  • 1 Surveillance, Epidemiology, and End Results Program. SEER Stat Fact Sheets: bladder cancer. http://seer.cancer.gov/statfacts/html/urinb.html (Zugriff am 10.5.2017)
  • 2 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Harnblasenkarzinoms, Langversion 1.1, 2016, AWMF-Registrierungsnummer 032/038OL. http://leitlinienprogramm-onkologie.de/Harnblasenkarzinom.92.0.html (Stand: 08.03.2017)
  • 3 Dash A. et al. Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer 2006; 107: 506-513
  • 4 http://www.asco.org/research-progress/reports-studies/clinical-cancer-advances/advance-year-immunotherapy-20 (Abruf am 10.3.2017)
  • 5 Fachinformation Tecentriq® . Stand: September 2017
  • 6 Balar AV. et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 2017; 389: 67-76
  • 7 Rosenberg JE. et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016; 387: 1909-1920
  • 8 Loriot Y. et al. Atezolizumab in Platinum-Treated Locally Advanced or Metastatic Urothelial Carcinoma (mUC): Updated OS, Safety and Biomarkers From the Phase II IMvigor210 Study. ESMO; 2016 abstr. 738P
  • 9 Fachinformation KEYTRUDA 25 mg/ml. Stand: August 2017
  • 10 OʼDonnell PH. et al. Biomarker findings and mature clinical results from KEYNOTE-052: First-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC). J Clin Oncol 2017; 35: 4502-4502 (suppl; abstr 4502); oral presentation (DOI: 10.1200/JCO.2017.35.15_suppl.4502, no. 15_suppl [May 2017])
  • 11 Bellmunt J. et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017; 376: 1015-1026
  • 12 Bajorin DF. et al. Planned survival analysis from KEYNOTE-045: Phase 3, open-label study of pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC). J Clin Oncol 2017; 35: 4501-4501 (suppl; abstr 4501); oral presentation (DOI: 10.1200/JCO.2017.35.15_suppl.4501, no. 15_suppl [May 2017])
  • 13 Perez-Gracia JL. et al. Atezolizumab (atezo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): outcomes by prior therapy. J Clin Oncol 2017; DOI: 10.1200/JCO.2017.35.6_suppl.323.
  • 14 Powles T, Durán I, van der Heijden MS. et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2017; DOI: 10.1016/S0140-6736(17)33297-X.
  • 15 Fachinformation OPDIVO® 10 mg/ml zur Herstellung von Infusionslösung. Stand: Juni 2017
  • 16 Sharma P. et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol 2017; 18 (3): 312-322 (DOI: 10.1016/S1470-2045(17)30065-7)
  • 17 Bellmunt J. et al. Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens. J Clin Oncol 2010; 28: 1850-1855
  • 18 Apolo AB. et al. Updated efficacy and safety of avelumab in metastatic urothelial carcinoma (mUC): Pooled analysis from 2 cohorts of the phase 1b Javelin solid tumor study. J Clin Oncol 2017; 35: 4528-4528
  • 19 Powles T. et al. Updated Efficacy and Tolerability of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma. J Clin Oncol 2017; DOI: 10.1200/JCO.2017.35.6_suppl.286.
  • 20 De Santis M. et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 2012; 30: 191-199
  • 21 Seymour L. et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 2017; 18 (3): e143-e152 (DOI: 10.1016/S1470-2045(17)30074-8)
  • 22 Bellmunt J. et al. IMvigor210: Updated Analyses of First-Line Atezolizumab in Cisplatin-Ineligible Locally Advanced/Metastatic Urothelial Carcinoma. ESMO; 2016 782PD (Poster)
  • 23 Foller S. et al. [Adverse events of immune checkpoint inhibitors]. Urologe A 2017; 56: 486-491
  • 24 Oppel-Heuchel H. et al. [Therapy monitoring and management of adverse events in PD-1/PD-L1 immune checkpoint inhibition]. Urologe A 2016; 55: 677-690
  • 25 Kumar V. et al. Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy. Front Pharmacol 2017; DOI: 10.3389/fphar.2017.00049.
  • 26 National Cancer Institute (2009). Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Abrufbar unter: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (Abruf am 16.03.2017)
  • 27 Pillai RN. et al. Evaluation of Toxicity Profile of PD-1 versus PD-L1 Inhibitors in Non-Small Cell Lung Cancer. Presented at the International Association for the study of Lung Cancer 17th World Conference on Lung Cancer; December 4–7, 2016; Vienna, Austria; abstr. 0A03.06
  • 28 Schmid P. et al. Association of PD-L2 expression in human tumors with atezolizumab activity. J Clin Oncol 2016; DOI: 10.1200/JCO.2016.34.15_suppl.11506.
  • 29 Callahan MK. et al. Evaluation of the clinical activity of ipilimumab (IPI) plus nivolumab (NIVO) in patients (pts) with NIVO-refractory metastatic urothelial cancer (UC). J Clin Oncol 2017; 35: 384-384 (suppl 6S; abstract 384) DOI: 10.1200/JCO.2017.35.6_suppl.384, no. 6_suppl [February 2017])