Skip to main content
SpringerLink
Log in

Systemtherapie des Nierenzellkarzinoms

Systemic treatment of renal cell carcinoma

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Die medikamentöse Behandlung des metastasierten Nierenzellkarzinoms (mRCC) hat sich in der letzten Dekade massiv verändert und wird sich weiterhin verändern.

Ziel

Im Folgenden soll ein Überblick über die gegenwärtige und zukünftige Behandlungssituation dargestellt werden.

Material und Methoden

Die Übersicht wurde unter Beachtung, Recherche und kritischer Interpretation der relevanten Phase-II- und -III-Studien (PubMed) sowie aktueller Kongressbeiträge (American Society of Clinical Oncology [ASCO], European Society of Medical Oncology [ESMO]) als auch der gegenwärtigen Leitlinien (S3, ESMO, National Comprehensive Cancer Network [NCCN]) erstellt.

Ergebnisse und Diskussion

Die gegenwärtige Behandlungssituation des mRCC befindet sich in massivem Wandel. Eine Risikostratifizierung nach IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) oder MSKCC (Memorial Sloan Kettering Cancer Center) ist zunehmend relevant für den klinischen Alltag. Gegenwärtig bleibt unter den medikamentösen Therapieoptionen die Inhibition des VEGFR (vaskulärer endothelialer Wachstumsfaktor-Rezeptor) die Standardoption für Patienten mit günstiger Prognose, die im Einzelfall auch für die intermediäre Gruppe eine Option darstellt. Die optimale Therapie für Patienten mit intermediärer und schlechter Prognose stellt die immunonkologische Doublettentherapie aus CTLA-4- und PD-1-Inhibition dar (PD-1 „programmed death receptor 1“, CTLA-4 „cytotoxic T‑lymphocyte associated protein 4“). Absehbar wird die Kombinationstherapie aus PD-1-Inhibition und VEGFR-Inhibition die Therapiemöglichkeiten im Alltag erweitern.

Abstract

Background

The pharmacological treatment of metastatic renal cell carcinoma (mRCC) has massively changed over the last decade and will continue to change in the future.

Objective

This article gives an overview of the current and future treatment situation.

Material and methods

This overview is based on the research and critical interpretation of the relevant phase II and phase III studies (PubMed), currently available congress articles, e.g. the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) and current guidelines, e.g. S3, ESMO and the National Comprehensive Cancer Network (NCCN).

Results and discussion

The current treatment situation for mRCC is in a state of massive flux. A risk stratification according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) model is becoming increasingly more relevant for the clinical routine. Currently, of the pharmacological treatment options vascular endothelial growth factor receptor (VEGFR) inhibition remains the standard option for patients with a favorable prognosis, which also represents an option for the intermediate group in individual cases. The optimal treatment for patients with intermediate and poor prognoses is immuno-oncological doublet treatment with CTLA-4 and PD-1. In the foreseeable future the combination treatment of PD-1 inhibition and VEGFR inhibition will extend the treatment options in the daily routine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Cella D, Escudier B, Tannir NM et al (2018) Quality of life outcomes for cabozantinib versus everolimus in patients with metastatic renal cell carcinoma: METEOR phase III randomized trial. J Clin Oncol 36:757–764. https://doi.org/10.1200/JCO.2017.75.2170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cella D, Grünwald V, Escudier B et al (2019) Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): A randomised, phase 3 trial. Lancet Oncol 20(2):297–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cella D, Grünwald V, Nathan P et al (2016) Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: A randomised, open-label, phase 3 trial. Lancet Oncol 17:994–1003. https://doi.org/10.1016/S1470-2045(16)30125-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Choueiri TK, Escudier B, Powles T et al (2015) Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1814–1823. https://doi.org/10.1056/NEJMoa1510016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Choueiri TK, Escudier B, Powles T et al (2016) Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): Final results from a randomised, open-label, phase 3 trial. Lancet Oncol 17:917–927. https://doi.org/10.1016/S1470-2045(16)30107-3

    Article  CAS  PubMed  Google Scholar 

  6. Choueiri TK, Halabi S, Sanford BL et al (2017) Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: The alliance A031203 CABOSUN trial. J Clin Oncol 35:591–597. https://doi.org/10.1200/JCO.2016.70.7398

    Article  CAS  PubMed  Google Scholar 

  7. Choueiri TK, Hessel C, Halabi S et al (2018) Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update. Eur J Cancer 94:115–125. https://doi.org/10.1016/j.ejca .2018.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Escudier B, Bellmunt J, Negrier S et al (2010) Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): Final analysis of overall survival. J Clin Oncol 28(13):2144–2150. https://doi.org/10.1200/JCO.2009.26.7849

    Article  CAS  PubMed  Google Scholar 

  9. Escudier B, Porta C, Bono P et al (2014) Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol 32:1412–1418. https://doi.org/10.1200/JCO.2013.50.8267

    Article  CAS  PubMed  Google Scholar 

  10. Escudier B, Porta C, Schmidinger M et al (2016) Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 27:v58–v68. https://doi.org/10.1093/annonc/mdw328

    Article  CAS  PubMed  Google Scholar 

  11. Escudier B, Tannir NM, McDermott DF et al (2017) LBA5: CheckMate 214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. Ann Oncol. https://doi.org/10.1093/annonc/mdx440.029

    Article  Google Scholar 

  12. Heng DYC, Xie W, Regan MM et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: Results from a large, multicenter study. J Clin Oncol 27:5794–5799. https://doi.org/10.1200/JCO.2008.21.4809

    Article  CAS  PubMed  Google Scholar 

  13. Heng DYC, Xie W, Regan MM et al (2013) External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: A population-based study. Lancet Oncol 14:141–148. https://doi.org/10.1016/S1470-2045(12)70559-4

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281. https://doi.org/10.1056/NEJMoa066838

    Article  CAS  PubMed  Google Scholar 

  15. Leitlinienprogramm Onkologie (Hrsg) (2017) S3-Leitlinie: Diagnostik, Therapie und Nachsorge des Nierenzellkarzinoms

    Google Scholar 

  16. Motzer RJ, Escudier B, McDermott DF et al (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1803–1813. https://doi.org/10.1056/NEJMoa1510665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Motzer RJ, Escudier B, Powles T et al (2018) Long-term follow-up of overall survival for cabozantinib versus everolimus in advanced renal cell carcinoma. Br J Cancer 118:1176–1178. https://doi.org/10.1038/s41416-018-0061-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Motzer RJ, Hutson TE, Cella D et al (2013) Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369:722–731. https://doi.org/10.1056/NEJMoa1303989

    Article  CAS  PubMed  Google Scholar 

  19. Motzer RJ, Hutson TE, Glen H et al (2015) Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: A randomised, phase 2, open-label, multicentre trial. Lancet Oncol 16:1473–1482. https://doi.org/10.1016/S1470-2045(15)00290-9

    Article  CAS  PubMed  Google Scholar 

  20. Motzer RJ, Hutson TE, McCann L et al (2014) Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med 370:1769–1770. https://doi.org/10.1056/NEJMc1400731

    Article  CAS  PubMed  Google Scholar 

  21. Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124. https://doi.org/10.1056/NEJMoa065044

    Article  CAS  PubMed  Google Scholar 

  22. Motzer RJ, Lee JL, Gurney H et al (2018) LBA6_PRJAVELIN renal 101: A randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). Ann Oncol. https://doi.org/10.1093/annonc/mdy424.036

    Article  PubMed  PubMed Central  Google Scholar 

  23. Motzer RJ, Nosov D, Eisen T et al (2013) Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: Results from a phase III trial. J Clin Oncol 31:3791–3799. https://doi.org/10.1200/JCO.2012.47.4940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Motzer RJ, Tannir NM, McDermott DF et al (2018) Nivolumab plus Ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378:1277–1290. https://doi.org/10.1056/NEJMoa1712126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Powles T, Albiges L, Staehler M et al (2018) Updated European Association of Urology Guidelines Recommendations for the treatment of first-line metastatic clear cell renal cancer. Eur Urol 3:11–13. https://doi.org/10.1016/J.EURURO.2017.11.016

    Article  Google Scholar 

  26. Rini BI, Halabi S, Rosenberg JE et al (2010) Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: Final results of CALGB 90206. J Clin Oncol 28:2137–2143. https://doi.org/10.1200/JCO.2009.26.5561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rini BI, Huseni M, Atkins MB et al (2018) LBA31Molecular correlates differentiate response to atezolizumab (atezo) + bevacizumab (bev) vs sunitinib (sun): Results from a phase III study (IMmotion151) in untreated metastatic renal cell carcinoma (mRCC). Ann Oncol. https://doi.org/10.1093/annonc/mdy424.037

    Article  Google Scholar 

  28. Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: Results of a randomized phase III trial. J Clin Oncol 28:1061–1068. https://doi.org/10.1200/JCO.2009.23.9764

    Article  CAS  PubMed  Google Scholar 

  29. Wiecek W, Karcher H (2016) Metastatic renal cell carcinoma. PLoS ONE 11:155389. https://doi.org/10.1371/journal.pone.0155389

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Deutschland

    P. Ivanyi

  2. Innere Klinik (Tumorforschung) und Klinik für Urologie, Schwerpunkt interdisziplinäre Uroonkologie, Westdeutsches Tumorzentrum, Universitätsklinikum Essen (AöR), OZ1, Raum 2.073, Hufelandstraße 55, 45147, Essen, Deutschland

    V. Grünwald

Authors
  1. P. Ivanyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. Grünwald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Grünwald.

Ethics declarations

Interessenkonflikt

P. Ivanyi: Beratung oder Gutachten: BMS, Bayer, EISAI, Ipsen, Merck, Novartis, Pfizer. Vortragshonorare: AIM, AstaZeneca, BMS, Bayer, EISAI, EUSA, Ipsen, Merck, MedKomAkademie, Novartis, Pfizer, Roche StreamedUP!. Forschungsförderung: BMS, Bayer, Lilly, Merck, Novartis, EISAI, Pfizer, MSD, AstraZeneca, Roche, Ipsen. Andere Finanzielle Beziehungen (Reisekostenzuschuss): BMS, Novartis, Merck, Ipsen, Bayer. Nichtfinanzielle Interessenkonflikte (Forschungsinteressen): mRCC, R/M-HNSCC, STS, PD-1, PDL1, PD-L2, cMET, Piwi-like, IO, PMSA, BAP1, NLR, CRP. V. Grünwald: Vortrags- und Beratungshonorare: Art tempi, AstraZeneca, Astellas, BMS, Cerulean, COCS, ClinSol, EUSAPharm, EISAI, lpsen, MedUpdate, Merck Serono, MSD Merck, MedKomAkademie, Novartis, NewConceptOncology, Lilly, Johnson & Johnson, PharmaMar, PeerVoice, Rache, StreamedUp!, ThinkWired!. Förderung: BMS, Novartis, EISAI, Pfizer, MSD, AstraZeneca, Rache, lpsen. Aktien- und Anteilsbesitz: AstraZeneca, BMS, MSD.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ivanyi, P., Grünwald, V. Systemtherapie des Nierenzellkarzinoms. Onkologe 25, 517–522 (2019). https://doi.org/10.1007/s00761-019-0566-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00761-019-0566-5

Schlüsselwörter

Keywords

Search

Navigation