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Advances in the Treatment of Metastatic Renal Cell Carcinoma

  • Paulo Bergerot
  • Kathy Burns
  • Dhruv Prajapati
  • Rachel Fox
  • Meghan Salgia
  • Sumanta K. Pal
Chapter
Part of the Cancer Treatment and Research book series (CTAR, volume 175)

Abstract

The treatment landscape for metastatic renal cell carcinoma has constantly been in flux. In 2005, with the advent of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy, the standard of care shifted to agents such as sunitinib and pazopanib. However, more recently there have been datasets, suggesting that next-generation TKIs such as cabozantinib may play an important role in therapy. Furthermore, immunotherapy has had resurgence with the FDA approval of nivolumab with ipilimumab. In the current chapter, we attempt to contextualize available frontline therapies for metastatic renal cell carcinoma with a focus on the CABOSUN and CheckMate 214 clinical trials.

Keywords

CheckMate 214 CABOSUN Metastatic 

Notes

Acknowledgements

None.

Conflict of Interest SKP declares consulting agreements with Genentech, Roche, Exelixis, BMS, Ipsen, Novartis, Astellas, Eisai and Pfizer.

References

  1. 1.
    Escudier B, Eisen T, Stadler WM et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. New Engl J Med 356:125–134CrossRefGoogle Scholar
  2. 2.
    Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. New Engl J Med 356:115–124CrossRefGoogle Scholar
  3. 3.
    Motzer RJ, Hutson TE, Cella D et al (2013) Pazopanib versus sunitinib in metastatic renal-cell carcinoma. New Engl J Med 369:722–731CrossRefGoogle Scholar
  4. 4.
    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: Official J Am Soc Clin Oncol 28:1061–1068CrossRefGoogle Scholar
  5. 5.
    Rini BI, Escudier B, Tomczak P, et al (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet (London, England) 378:1931–1939CrossRefGoogle Scholar
  6. 6.
    Escudier B, Pluzanska A, Koralewski P, et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet (London, England) 370:2103–2111CrossRefGoogle Scholar
  7. 7.
    Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. New Engl J Med 356:2271–2281CrossRefGoogle Scholar
  8. 8.
    Motzer RJ, Escudier B, Oudard S, et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet (London, England) 372:449–456CrossRefGoogle Scholar
  9. 9.
    Atzpodien J, Kirchner H, Jonas U et al (2004) Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). J Clin Oncol: Official J Am Soc Clin Oncol 22:1188–1194CrossRefGoogle Scholar
  10. 10.
    Pal SK, Bergerot P, Figlin RA (2015) Renal cell carcinoma: An update for the practicing urologist. Asian J Urol 2:19–25CrossRefGoogle Scholar
  11. 11.
    Choueiri TK, Motzer RJ (2017) Systemic therapy for metastatic renal-cell carcinoma. New Engl J Med 376:354–366CrossRefGoogle Scholar
  12. 12.
    Singh P, Agarwal N, Pal SK (2015) Sequencing systemic therapies for metastatic kidney cancer. Curr Treat Options Oncol 16:316CrossRefGoogle Scholar
  13. 13.
    McDermott DF (2011) Immunotherapy and targeted therapy combinations in renal cancer. Current Clin Pharmacool 6:207–213CrossRefGoogle Scholar
  14. 14.
    Albouy B, Gross Goupil M, Escudier B, Massard C (2010) Renal cell carcinoma management and therapies in 2010. Bull Cancer 97:17–28PubMedGoogle Scholar
  15. 15.
    Ho TH, Choueiri TK, Wang K et al (2016) Correlation between molecular subclassifications of clear cell renal cell carcinoma and targeted therapy response. Eur Urol Focus 2:204–209 CrossRefGoogle Scholar
  16. 16.
    Cancer Genome Atlas Research Network (2013) Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499:43–49 Google Scholar
  17. 17.
    Pal SK, Signorovitch JE, Li N et al (2017) Patterns of care among patients receiving sequential targeted therapies for advanced renal cell carcinoma: A retrospective chart review in the USA. Int J Urol: Official J Jpn Urol Assoc 24:272–278CrossRefGoogle Scholar
  18. 18.
    Hammers HJ, Plimack ER, Sternberg C, et al (2015) 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 33:TPS4578–TPSGoogle Scholar
  19. 19.
    Heng DY, 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: Official J Am Soc Clin Oncol 27:5794–5799CrossRefGoogle Scholar
  20. 20.
    Motzer RJ, Tannir NM, McDermott DF, Frontera OA, Melichar B, Plimack ER, Barthelemy P, George S, Neiman V, Porta C, Choueiri TK, Powles T, Donskov F, Salman P, Kollmannsberger CK, Rini B, Mekan S, McHenry MB, Wind‐Rotolo M, Hammers HJ, Escudier B (2017) Nivolumab + Ipilimumab (N + I) versus Sunitinib (S) for treatment‐naïve advanced or metastatic renal cell carcinoma (aRCC): results from CheckMate 214, including overall survival by subgroups. SITC 2017 ANNUAL MEETING ABSTRACTS BOOK. Maryland: Society for Immunotherapy of Cancer p 103Google Scholar
  21. 21.
    Choueiri TK, Escudier B, Powles T et al (2015) Cabozantinib versus everolimus in advanced renal-cell carcinoma. New Engl J Med 373:1814–1823CrossRefGoogle Scholar
  22. 22.
    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 35:591–597CrossRefGoogle Scholar
  23. 23.
    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 17:917–927CrossRefGoogle Scholar
  24. 24.
    NIH U.S. National library of medicine https://clinicaltrials.gov/ Accessed January 10, 2018
  25. 25.
    Choueiri TK, Rini BI, Larkin JMG, et al (2017) Avelumab plus axitinib versus sunitinib as first-line treatment of advanced renal cell carcinoma: Phase 3 study (JAVELIN Renal 101). J Clin Oncol 35:TPS4594–TPSCrossRefGoogle Scholar
  26. 26.
    Atkins MB, Gupta S, Choueiri TK et al (2015) Phase Ib dose-finding study of axitinib plus pembrolizumab in treatment-naïve patients with advanced renal cell carcinoma. J Immuno Ther Cancer 3:353CrossRefGoogle Scholar
  27. 27.
    Lee CVM, Rasco D, Taylor M, Dutcus C, Shumaker R., Schmidt EV, Stepan D., Li D, Motzer RJ (2017) Anti-Cancer Agents & Biologic Therapy Renal Cell Cancer Cancer Immunology and Immunotherapy Genitourinary Cancers. ESMO 2017 Congress. Madrid, Spain: Annals of Oncology v295–v329. 10.1093Google Scholar
  28. 28.
    Hahn AW, Gill DM, Maughan B et al (2017) Correlation of genomic alterations assessed by next-generation sequencing (NGS) of tumor tissue DNA and circulating tumor DNA (ctDNA) in metastatic renal cell carcinoma (mRCC): potential clinical implications. Oncotarget 8:33614–33620PubMedPubMedCentralGoogle Scholar
  29. 29.
    Becerra MF, Reznik E, Redzematovic A, et al (2017) Comparative genomic profiling of matched primary and metastatic tumors in renal cell carcinoma. Eur Urol FocusGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Paulo Bergerot
    • 1
  • Kathy Burns
    • 1
  • Dhruv Prajapati
    • 1
  • Rachel Fox
    • 1
  • Meghan Salgia
    • 1
  • Sumanta K. Pal
    • 1
  1. 1.Department of Medical Oncology and Therapeutics ResearchCity of Hope Comprehensive Cancer CenterDuarteUSA

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