Skip to main content
SpringerLink
Log in

Targeted Therapies for Treatment of Metastatic Renal Cell Carcinoma

  • Chapter
  • First Online:
Chemotherapy and Immunotherapy in Urologic Oncology

  • 516 Accesses

Abstract

Metastatic renal cell carcinoma historically resulted in poor patient outcomes. With the discovery of the von Hippel-Lindau gene and its relationship to kidney cancer, targeted therapies were developed as a viable and useful treatment option. The landmark trials testing these therapies are reviewed in detail, and treatment indications, benefits, and limitations will be discussed. Finally, we will review management of treatment side effects, as allowing patients to continue treatment regimens and maintaining or improving their overall quality of life are the ultimate goals.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Linehan WM, Bratslavsky G, Pinto PA, Schmidt LS, Neckers L, Bottaro DP, et al. Molecular diagnosis and therapy of kidney cancer. Annu Rev Med. 2010;61:329–43. https://doi.org/10.1146/annurev.med.042808.171650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Janzen NK, Kim HL, Figlin RA, Belldegrun AS. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am. 2003;30(4):843–52.

    Article  Google Scholar 

  3. Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993;260(5112):1317–20.

    Article  CAS  Google Scholar 

  4. Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P, et al. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol. 2005;23(4):832–41. https://doi.org/10.1200/JCO.2005.05.179.

    Article  PubMed  Google Scholar 

  5. Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol. 1984;2(3):187–93. https://doi.org/10.1200/JCO.1984.2.3.187.

    Article  CAS  PubMed  Google Scholar 

  6. Cohen HT, McGovern FJ. Renal cell carcinoma. N Engl J Med. 2005;353:2477–90.

    Article  CAS  Google Scholar 

  7. Practice guidelines in oncology: kidney cancer. [database on the Internet] Version 2.2019. Accessed. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf.

  8. Awada A, Hendlisz A, Gil T, Bartholomeus S, Mano M, de Valeriola D, et al. Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer. 2005;92(10):1855–61. https://doi.org/10.1038/sj.bjc.6602584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(8):1280–9. https://doi.org/10.1200/JCO.2008.19.3342.

    Article  CAS  PubMed  Google Scholar 

  10. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009;27(20):3312–8. https://doi.org/10.1200/JCO.2008.19.5511.

    Article  CAS  PubMed  Google Scholar 

  11. Bayer. Nexavar (sorafenib). Prescribing information. 2005.

    Google Scholar 

  12. Motzer RJ, McCann L, Deen K. Pazopanib versus sunitinib in renal cancer. N Engl J Med. 2013;369(20):1970. https://doi.org/10.1056/NEJMc1311795.

    Article  PubMed  Google Scholar 

  13. Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014;370(18):1769–70. https://doi.org/10.1056/NEJMc1400731.

    Article  CAS  PubMed  Google Scholar 

  14. Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008;26(1):127–31. https://doi.org/10.1200/JCO.2007.13.3223.

    Article  CAS  PubMed  Google Scholar 

  15. Lee JL, Ahn JH, Lim HY, Park SH, Lee SH, Kim TM, et al. Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma. Ann Oncol. 2012;23(8):2108–14. https://doi.org/10.1093/annonc/mdr586.

    Article  PubMed  Google Scholar 

  16. Ltd. P. Sutent (sunitinib malate). Highlights of prescribing information. 2006.

    Google Scholar 

  17. Novartis. Afinitor (everolimus). Highlights of prescribing information. 2009.

    Google Scholar 

  18. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061–8. https://doi.org/10.1200/JCO.2009.23.9764.

    Article  CAS  PubMed  Google Scholar 

  19. Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, et al. 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. 2014;32(14):1412–8. https://doi.org/10.1200/JCO.2013.50.8267.

    Article  CAS  PubMed  Google Scholar 

  20. GlaxoSmithKline. Votrient (pazopanib). Summary of product characteristics. 2009.

    Google Scholar 

  21. Choueiri TK, Halabi S, Sanford BL, Hahn O, Michaelson MD, Walsh MK, et al. 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. 2017;35(6):591–7. https://doi.org/10.1200/JCO.2016.70.7398.

    Article  CAS  PubMed  Google Scholar 

  22. Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(7):917–27. https://doi.org/10.1016/S1470-2045(16)30107-3.

    Article  CAS  PubMed  Google Scholar 

  23. Exelexis. Cabometyx (cabozantinib). Highlights of prescribing information. 2012.

    Google Scholar 

  24. Rini BI, Melichar B, Ueda T, Grünwald V, Fishman MN, Arranz JA, et al. Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial. Lancet Oncol. 2013;14(12):1233–42. https://doi.org/10.1016/S1470-2045(13)70464-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013;14(13):1287–94. https://doi.org/10.1016/S1470-2045(13)70465-0.

    Article  CAS  PubMed  Google Scholar 

  26. Pfizer. Inlyta (axitinib). Highlights of prescribing information. 2012.

    Google Scholar 

  27. Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013;49(6):1287–96. https://doi.org/10.1016/j.ejca.2012.12.010.

    Article  CAS  PubMed  Google Scholar 

  28. Hartmann JT, Haap M, Kopp HG, Lipp HP. Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects. Curr Drug Metab. 2009;10(5):470–81.

    Article  CAS  Google Scholar 

  29. Krajewski KM, Nishino M, Ramaiya NH, Choueiri TK. RECIST 1.1 compared with RECIST 1.0 in patients with advanced renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy. AJR Am J Roentgenol. 2015;204(3):W282–8. https://doi.org/10.2214/AJR.14.13236.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L, et al. 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. 2010;28(13):2137–43. https://doi.org/10.1200/JCO.2009.26.5561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931–9. https://doi.org/10.1016/S0140-6736(11)61613-9.

    Article  CAS  PubMed  Google Scholar 

  32. Genentech. Avastin (bevacizumab). Highlights of prescribing information. 2004.

    Google Scholar 

  33. Harshman LC, Srinivas S. The bevacizumab experience in advanced renal cell carcinoma. Onco Targets Ther. 2010;3:179–89.

    Article  CAS  Google Scholar 

  34. Xie J, Wang X, Proud CG. mTOR inhibitors in cancer therapy. F1000Res. 2016;5 https://doi.org/10.12688/f1000research.9207.1.

  35. Hwang C, Heath EI. The judgment of Paris: treatment dilemmas in advanced renal cell carcinoma. J Clin Oncol. 2014;32(8):729–34. https://doi.org/10.1200/JCO.2013.53.6029.

    Article  CAS  PubMed  Google Scholar 

  36. Pfizer. Torisel (temsirolimus). Highlights of prescribing information. 2007.

    Google Scholar 

  37. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372(9637):449–56. https://doi.org/10.1016/S0140-6736(08)61039-9.

    Article  CAS  PubMed  Google Scholar 

  38. Escudier B, Sharma P, McDermott DF, George S, Hammers HJ, Srinivas S, et al. CheckMate 025 randomized phase 3 study: outcomes by key baseline factors and prior therapy for Nivolumab versus Everolimus in advanced renal cell carcinoma. Eur Urol. 2017;72(6):962–71. https://doi.org/10.1016/j.eururo.2017.02.010.

    Article  CAS  PubMed  Google Scholar 

  39. Buti S, Leonetti A, Dallatomasina A, Bersanelli M. Everolimus in the management of metastatic renal cell carcinoma: an evidence-based review of its place in therapy. Core Evid. 2016;11:23–36. https://doi.org/10.2147/CE.S98687.

    Article  PubMed  PubMed Central  Google Scholar 

  40. George S, Bukowski R. Role of everolimus in the treatment of renal cell carcinoma. Therapeutics and Clinical Risk Management. 2009;5:699–706.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urologic Oncology, Temple University Hospital, Philadelphia, PA, USA

    Jessica Matande & Adam C. Reese

Authors
  1. Jessica Matande
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adam C. Reese
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jessica Matande .

Editor information

Editors and Affiliations

  1. Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA

    Edouard J. Trabulsi

  2. Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA

    Costas D. Lallas

  3. Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA

    Anne E. Lizardi-Calvaresi

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Matande, J., Reese, A.C. (2021). Targeted Therapies for Treatment of Metastatic Renal Cell Carcinoma. In: Trabulsi, E.J., Lallas, C.D., Lizardi-Calvaresi, A.E. (eds) Chemotherapy and Immunotherapy in Urologic Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-52021-2_21

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-52021-2_21

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-52020-5

  • Online ISBN: 978-3-030-52021-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation