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Second-line treatment for metastatic clear cell renal cell cancer: experts’ consensus algorithms

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Abstract

Background

Second-line systemic treatment options for metastatic clear cell renal cell cancer (mccRCC) are diverse and treatment strategies are variable among experts. Our aim was to investigate the approach for the second-line treatment after first-line therapy with a tyrosine kinase inhibitor (TKI). Recently two phase III trials have demonstrated a potential role for nivolumab (NIV) and cabozantinib (CAB) in this setting. We aimed to estimate the impact of these trials on clinical decision making.

Materials and methods

Eleven international experts were asked to provide their treatment strategies for second-line systemic therapy for mccRCC in the current setting and once NIV and CAB will be approved and available. The treatment strategies were analyzed with the objective consensus approach.

Results

The analysis of the decision trees revealed everolimus (EVE), axitinib (AXI), NIV and TKI switch (sTKI) as therapeutic options after first-line TKI therapy in the current situation and mostly NIV and CAB in the future setting. The most commonly used criteria for treatment decisions were duration of response, TKI tolerance and zugzwang a composite of several related criteria.

Conclusion

In contrast to the first-line setting, recommendations for second-line systemic treatment of mccRCC among experts were not as heterogeneous. The agents mostly used after disease progression on a first-line TKI included: EVE, AXI, NIV and sTKI. In the future setting of NIV and CAB availability, NIV was the most commonly chosen drug, whereas several experts identified situations where CAB would be preferred.

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References

  1. Escudier B, Porta C, Schmidinger M, Algaba F, Patard JJ, Khoo V, Eisen T, Horwich A, Group EGW (2014) Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(3):49–56. doi:10.1093/annonc/mdu259

    Google Scholar 

  2. Ouzaid I, Rini B (2014) Words of wisdom: re: Pazopanib versus sunitinib in metastatic renal-cell carcinoma. Eur Urol 65(3):667–668. doi:10.1016/j.eururo.2013.11.023

    Article  CAS  PubMed  Google Scholar 

  3. Rothermundt C, Bailey A, Cerbone L, Eisen T, Escudier B, Gillessen S, Grunwald V, Larkin J, McDermott D, Oldenburg J, Porta C, Rini B, Schmidinger M, Sternberg C, Putora PM (2015) Algorithms in the first-line treatment of metastatic clear cell renal cell carcinoma-analysis using diagnostic nodes. Oncologist 20(9):1028–1035. doi:10.1634/theoncologist.2015-0145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378(9807):1931–1939. doi:10.1016/s0140-6736(11)61613-9

    Article  CAS  PubMed  Google Scholar 

  5. Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ (2014) Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 32(8):760–767. doi:10.1200/JCO.2013.50.3961

    Article  CAS  PubMed  Google Scholar 

  6. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A, Group R-S (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116(18):4256–4265. doi:10.1002/cncr.25219

    Article  Google Scholar 

  7. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P, CheckMate I (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373(19):1803–1813. doi:10.1056/NEJMoa1510665

    Article  CAS  PubMed  Google Scholar 

  8. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ (2015) Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373(19):1814–1823. doi:10.1056/NEJMoa1510016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DY, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ, investigators M (2016) Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. doi:10.1016/S1470-2045(16)30107-3

    PubMed  Google Scholar 

  10. Putora PM, Panje CM, Papachristofilou A, Dal Pra A, Hundsberger T, Plasswilm L (2014) Objective consensus from decision trees. Radiat Oncol 9:270. doi:10.1186/s13014-014-0270-y

    Article  PubMed  PubMed Central  Google Scholar 

  11. Panje CM, Dal Pra A, Zilli T, RZ D, Papachristofilou A, Herrera FG, Matzinger O, Plasswilm L, Putora PM (2015) Consensus and differences in primary radiotherapy for localized and locally advanced prostate cancer in Switzerland: a survey on patterns of practice. Strahlenther Onkol 191(10):778–786. doi:10.1007/s00066-015-0849-8

    Article  PubMed  Google Scholar 

  12. Hundsberger T, Hottinger AF, Roelcke U, Roth P, Migliorini D, Dietrich PY, Conen K, Pesce G, Hermann E, Pica A, Gross MW, Brugge D, Plasswilm L, Weller M, Putora PM (2016) Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes. J Neurooncol 126(1):175–183. doi:10.1007/s11060-015-1957-0

    Article  CAS  PubMed  Google Scholar 

  13. wikipedia zugzwang (2016) https://en.wikipedia.org/wiki/Zugzwang. Accessed 17 Feb 2016

  14. Ljungberg B, Bensalah K, Bex A, Canfield S, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Lam T, Marconi L, Merseburger AS, Powles T, Staehler M, Volpe A (2016) Renal cell carcinoma. https://uroweb.org/guideline/renal-cell-carcinoma/?type=pocket-guidelines. Accessed 28 June 2016

  15. Powles T, Staehler M, Ljungberg B, Bensalah K, Canfield SE, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA (2016) European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy. European Urology. doi:10.1016/j.eururo.2016.06.009

    Google Scholar 

  16. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim H-J, Wood K, Dutcus C, Larkin J (2015) Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol 16(15):1473–1482. doi:10.1016/s1470-2045(15)00290-9

    Article  CAS  PubMed  Google Scholar 

  17. Motzer RJ, Hutson TE, Ren M, Dutcus C, Larkin J (2016) Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol 17(1):e4–e5. doi:10.1016/s1470-2045(15)00543-4

    Article  PubMed  Google Scholar 

  18. Research CfDEa (2016) Approved drugs—lenvatinib in combination with everolimus. Center for Drug Evaluation and Research. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm501070.htm. Accessed 29 June 2016

  19. Fischer S, Gillessen S, Rothermundt C (2015) Sequence of treatment in locally advanced and metastatic renal cell carcinoma. Transl Androl Urol 4(3):310–325. doi:10.3978/j.issn.2223-4683.2015.04.07

    PubMed  PubMed Central  Google Scholar 

  20. Nadal R, Amin A, Geynisman DM, Voss MH, Weinstock M, Doyle J, Zhang Z, Viudez A, Plimack ER, McDermott DF, Motzer R, Rini B, Hammers HJ (2016) Safety and clinical activity of vascular endothelial growth factor receptor (VEGFR)- tyrosine kinase inhibitors after programmed cell death 1 inhibitor treatment in patients with metastatic clear cell renal cell carcinoma. Ann Oncol Off J Eur Soc Med Oncol ESMO. doi:10.1093/annonc/mdw160

    Google Scholar 

  21. Burotto M, Wilkerson J, Stein W, Motzer R, Bates S, Fojo T (2014) Continuing a cancer treatment despite tumor growth may be valuable: sunitinib in renal cell carcinoma as example. PLoS One 9(5):e96316. doi:10.1371/journal.pone.0096316

    Article  PubMed  PubMed Central  Google Scholar 

  22. Quinn DI, Lara PN Jr (2015) Renal-cell cancer—targeting an immune checkpoint or multiple kinases. N Engl J Med. doi:10.1056/NEJMe1511252

  23. Umeweni N, Mikudina B, Sutcliffe F, Stevens A (2015) NICE guidance on axitinib for treating advanced renal cell carcinoma after failure of prior systemic treatment. Lancet Oncol 16(4):367–368. doi:10.1016/s1470-2045(14)70484-x (Epub 2015 Feb 25)

    Article  CAS  PubMed  Google Scholar 

  24. Putora PM, Oldenburg J (2013) Swarm-based medicine. J Med Internet Res 15(9):e207. doi:10.2196/jmir.2452

    Article  PubMed  PubMed Central  Google Scholar 

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Authors’ contributions

C. Rothermundt, J. von Rappard and PM. Putora involved in protocol/project development, data collection and management, data analysis, manuscript writing and editing, primary analysis and interpretation of the data. T. Eisen, B. Escudier, V. Grünwald, J. Larkin, D. McDermott, J. Oldenburg, C. Porta, B. Rini, M. Schmidinger and CN. Sternberg contributed to data collection and management, data analysis, manuscript writing and editing.

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Authors and Affiliations

  1. Department of Haematology and Oncology, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland

    C. Rothermundt

  2. Department of Nephrology, University Hospital Bern, Bern, Switzerland

    J. von Rappard

  3. Department of Oncology, Cambridge University Hospitals NHS Foundation Cambridge, Cambridge, UK

    T. Eisen

  4. Gustave Roussy, Villejuif, France

    B. Escudier

  5. Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany

    V. Grünwald

  6. The Royal Marsden Hospital, London, UK

    J. Larkin

  7. Beth Israel Deaconess Medical Center, Boston, MA, USA

    D. McDermott

  8. Department of Medical Oncology, Norwegian Radium Hospital, Oslo, Norway

    J. Oldenburg

  9. Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy

    C. Porta

  10. Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH, USA

    B. Rini

  11. Abteilung für Onkologie, Allgemeines Krankenhaus, Universitätskliniken, Vienna, Austria

    M. Schmidinger

  12. Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy

    C. N. Sternberg

  13. Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland

    P. M. Putora

Authors
  1. C. Rothermundt
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  2. J. von Rappard
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  3. T. Eisen
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  4. B. Escudier
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  5. V. Grünwald
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  6. J. Larkin
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  7. D. McDermott
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  8. J. Oldenburg
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  9. C. Porta
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  10. B. Rini
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  11. M. Schmidinger
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  12. C. N. Sternberg
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  13. P. M. Putora
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Corresponding author

Correspondence to C. Rothermundt.

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Conflict of interest

Rothermundt C Pfizer (Consultant Scientific Advisory Board), GSK (Symposium funding–Personal fees), Novartis (Symposium funding–Personal fees); von Rappard J None; Eisen T AstraZeneca (Grant-Employment since 01/09/2014), Novartis (Personal Fees), Bayer (Grant), Pfizer (Gant and Personal fees), GSK (Personal fees), Roche (Personal fees), BMS (Personal fees), AVEO (Personal fees–TMG), Astella (Personal fees–TMG); Escudier B None; Grünwald V Bayer (Personal fees Lecture), GSK (Personal fees Lecture and Advisor), Novartis (Personal fees Lecture and Advisor), Pfizer (Personal fees Lecture and Advisor); Larkin J None; McDermott D Roche (Personal fees), Pfizer (Personal fees), BMS (Personal fees), Merck (Personal fees); Oldenburg J None; Porta C Pfizer (Grant and personal fees), GSK (Personal fees), Bayer (Personal fees), Novartis (Grant, personal fees and non-financial support), Astellas (Grant), Pierre Fabre (Grant); Rini B Pfizer (Consulting and research funding); Schmidinger M Pfizer (Lectures and consultancy), GSK (Lectures and consultancy), Roche (Lectures and consultancy), Astellas (Lectures and consultancy), Novartis (Lectures and consultancy; Sternberg C Pfizer (Honoraria), Novartis (Honoraria); Putora PM None.

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Rothermundt, C., von Rappard, J., Eisen, T. et al. Second-line treatment for metastatic clear cell renal cell cancer: experts’ consensus algorithms. World J Urol 35, 641–648 (2017). https://doi.org/10.1007/s00345-016-1903-6

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  • DOI: https://doi.org/10.1007/s00345-016-1903-6

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