Skip to main content

Advertisement

SpringerLink
Log in

Best treatment options for advanced renal cell carcinoma (RCC) patients: a Delphi consensus study

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The introduction of targeted therapy for the treatment of advanced renal cell carcinoma (RCC) has improved the outcome of these patients in the last decade. However, many patients still relapse. The aim of this consensus study was to establish common recommendations about the best treatment options in patients with RCC. A two-round Delphi methodology was used. A total of 25 statements were submitted to a panel of 30 specialists. If consensus was not obtained in the first round a second and last round was performed. Agreement was achieved for 19 of the proposed 25 statements (76%). When making a decision about the treatment option, considering the efficiency and response rate to previous treatment, drug’s toxicity and the patients’ clinical features are very relevant.

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

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2017;2017;67:7–30. https://doi.org/10.3322/caac.21387.

    Article  PubMed  Google Scholar 

  2. Barata PC, Rini BI. Treatment of renal cell carcinoma: current status and future directions. CA Cancer J Clin. 2017;67:507–24. https://doi.org/10.3322/caac.21411.

    Article  PubMed  Google Scholar 

  3. Sanfrancesco JM, Cheng L. Complexity of the genomic landscape of renal cell carcinoma: implications for targeted therapy and precision immuno-oncology. Crit Rev Oncol Hematol. 2017;119:23–8. https://doi.org/10.1016/j.critrevonc.2017.09.011.

    Article  PubMed  Google Scholar 

  4. Tannir NM, Pal SK, Atkins MB. Second-line treatment landscape for renal cell carcinoma: a comprehensive review. Oncologist. 2018;23:540–55. https://doi.org/10.1634/theoncologist.2017-0534.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Osorio JC, Motzer RJ, Voss MH. Optimizing treatment approaches in advanced renal cancer. Oncology (Williston Park). 2017;31:919–26.

    Google Scholar 

  6. Kaelin WG Jr. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer. 2008;8:865–73. https://doi.org/10.1038/nrc2502.

    Article  CAS  PubMed  Google Scholar 

  7. Battelli C, Cho DC. mTOR inhibitors in renal cell carcinoma. Therapy. 2011;8:359–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Carlo MI, Voss MH, Motzer RJ. Checkpoint inhibitors and other novel immunotherapies for advanced renal cell carcinoma. Nat Rev Urol. 2016;13:420–31. https://doi.org/10.1038/nrurol.2016.103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Choueiri TK, Motzer RJ. Systemic therapy for metastatic renal-cell carcinoma. N Engl J Med. 2017;376:354–66. https://doi.org/10.1056/NEJMra1601333.

    Article  CAS  PubMed  Google Scholar 

  10. 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;17:917–27. https://doi.org/10.1016/S1470-2045(16)30175-9.

    Article  CAS  PubMed  Google Scholar 

  11. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S. et al.. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13. https://doi.org/10.1056/NEJMoa1510665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kouba EJ, Eble JN, Simper N, Grignon DJ, Wang M, Zhang S, et al. High fidelity of driver chromosomal alterations among primary and metastatic renal cell carcinomas: implications for tumor clonal evolution and treatment. Mod Pathol. 2016;29:1347–57. https://doi.org/10.1038/modpathol.2016.133.

    Article  PubMed  Google Scholar 

  13. Diamond IR, Grant RC, Feldman BM, Pencharz PB, Ling SC, Moore AM, et al. Defining consensus: a systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol. 2014;67(4):401–9. https://doi.org/10.1016/j.jclinepi.2013.12.002.

    Article  PubMed  Google Scholar 

  14. Fitch K, Bernstein SJ, Aguilar MD, Burnand B, LaCalle JR, Lazaro P, et al. The RAND/UCLA appropriateness method user’s manual. Santa Monica: RAND Corporation; 2001. https://www.rand.org/pubs/monograph_reports/MR1269.html.

  15. Jones J, Hunter D. Consensus methods for medical and health services research. BMJ. 1995;311:376–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chaudhari PB. Nivolumab—Pearls of evidence. Indian J Med Paediatr Oncol. 2017;38:520–5. https://doi.org/10.4103/ijmpo.ijmpo_193_16.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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;72:962–71. https://doi.org/10.1016/j.eururo.2017.02.010.

    Article  CAS  PubMed  Google Scholar 

  18. Hamid O, Carvajal RD. Anti-programmed death-1 and anti-programmed death-ligand 1 antibodies in cancer therapy. Expert Opin Biol Ther. 2013;13:847–61. https://doi.org/10.1517/14712598.2013.770836.

    Article  CAS  PubMed  Google Scholar 

  19. Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006;66:3381–5. https://doi.org/10.1158/0008-5472.CAN-05-4303.

    Article  CAS  PubMed  Google Scholar 

  20. Hasskarl J. Everolimus. Recent Results Cancer Res. 2014;201:373–92. https://doi.org/10.1007/978-3-642-54490-3_23.

    Article  CAS  PubMed  Google Scholar 

  21. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10:2298–308. https://doi.org/10.1158/1535-7163.MCT-11-0264.

    Article  CAS  PubMed  Google Scholar 

  22. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1814–23. https://doi.org/10.1056/NEJMoa1510016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015;16:1473–82. https://doi.org/10.1016/S1470-2045(15)00290-9.

    Article  CAS  PubMed  Google Scholar 

  24. Motzer RJ, Hutson TE, Ren M, Dutcus C, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016;17(1):e4–5. https://doi.org/10.1016/S1470-2045(15)00543-4.

    Article  PubMed  Google Scholar 

  25. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125–34. https://doi.org/10.1056/NEJMoa060655.

    Article  CAS  PubMed  Google Scholar 

  26. 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;372:449–56. https://doi.org/10.1016/S0140-6736(08)61039-9.

    Article  CAS  PubMed  Google Scholar 

  27. 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;378:1931–39. https://doi.org/10.1016/S0140-6736(11)61613-9.

    Article  CAS  PubMed  Google Scholar 

  28. Cella D, Escudier B, Rini B, Chen C, Bhattacharyya H, Tarazi J, et al. Patient-reported outcomes for axitinib vs sorafenib in metastatic renal cell carcinoma: phase III (AXIS) trial. Br J Cancer. 2013;108:1571–8. https://doi.org/10.1038/bjc.2013.145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Escudier B, Michaelson MD, Motzer RJ, Hutson TE, Clark JI, Lim HY, et al. Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomised phase III trial. Br J Cancer. 2014 Jun;10(12):2821–8. https://doi.org/10.1038/bjc.2014.244. 110) .

    Article  CAS  Google Scholar 

  30. Long GV, Tykodi SS, Schneider JG, Garbe C, Gravis G, Rashford M, et al. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018;29(11):2208–13. https://doi.org/10.1093/annonc/mdy408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–90. https://doi.org/10.1056/NEJMoa1712126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Weber J. Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist. 2007;12:864–72. https://doi.org/10.1634/theoncologist.12-7-864.

    Article  CAS  PubMed  Google Scholar 

  33. 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 

Download references

Acknowledgements

Authors would like to acknowledge their contribution to the participating panelists who have voted the statements following the Delphi methodology: Ignacio Durán, Emilio Esteban, Javier Puente, Isabel Chirivella, Aránzazu González del Alba, Nuria Láinez, Xavier Garcia del Muro, Pablo Maroto, Julio Lambea, Enrique González Billalabeitia, Marilo Torregrosa, Carmen Santander, Alvaro Pinto, Mª José Juan, Enrique Gallardo, Sergio Vázquez, Mª José Méndez Vidal, Juan Francisco Rodríguez, Jesús García Donas, Alejo Rodríguez-Vida, Begoña Pérez-Valderrama, Martín Lázaro, Ignacio Peláez. The authors would like to acknowledge Dr. Pablo Rivas and Dr. Idoia Garcia who provided medical writing support on behalf of Springer Healthcare, with funding from Bristol Myers Squibb.

Funding

Bristol-Myers Squibb promoted and financed this study without participating in its design, analysis of data, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain

    José Luis Pérez-Gracia

  2. Department of Uro-oncology, Hospital Universitario 12 de Octubre, Madrid, Spain

    Daniel Castellano

  3. Department of Medical Oncology, Instituto Valenciano de Oncología (IVO), Valencia, Spain

    Miguel Ángel Climent

  4. Department of Medical Oncology, Hospital Clinic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain

    Begoña Mellado

  5. Department of Medical Oncology, Vall d’Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

    Cristina Suárez

Authors
  1. José Luis Pérez-Gracia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Castellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miguel Ángel Climent
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Begoña Mellado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cristina Suárez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Luis Pérez-Gracia.

Ethics declarations

Conflict of interest

Authors declare no conflicts of interest regarding this study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pérez-Gracia, J.L., Castellano, D., Climent, M.Á. et al. Best treatment options for advanced renal cell carcinoma (RCC) patients: a Delphi consensus study. Med Oncol 36, 29 (2019). https://doi.org/10.1007/s12032-019-1251-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-019-1251-7

Keywords

Search

Navigation