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Redefiniendo el Tratamiento del Cáncer Renal

Explore the latest advancements in renal cancer treatment, including active surveillance, metastasectomy, cytoreductive nephrectomy, and systemic treatment options. Discover the potential of immunotherapy and targeted therapy in improving patient outcomes.

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Redefiniendo el Tratamiento del Cáncer Renal

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  1. Redefiniendo el Tratamiento del Cáncer Renal Enrique Grande Head of Medical Oncology Director of Clinical Research

  2. Disclosures Honoraria for ad boards and/or lectures: Pfizer, BMS, IPSEN, Roche, Eisai, Eusa Pharma, MSD, Sanofi-Genzyme, Adacap, Novartis, Pierre Fabre, Lexicon, Celgene Research Grants: Pfizer, Astra Zeneca, MTEM/Threshold, Roche, IPSEN, Lexicon Leadership roles in medical societies: ENETS, GETNE and GETHI Stocks or ownership interest: None

  3. Pathways and Current Drugs in Metastatic RCC Choueiri & Motzer. NEnglJMed 2017

  4. Curti BD. NEnglJMed 2018

  5. Survival, Durable Response, and Long-Term Safety inPatients With Advanced RCC Receiving Nivolumab Rini B, et al. 13th European International KidneyCancerSymposium;April 27–28, 2018; Prague, Czech Republic

  6. Spontaneous Regression in Renal Cancer Bloom & Wallace. Br MedJ 1964

  7. ’Real World’ Immuno-Oncology Sequences Presented By Daniel Heng at 2019 Genitourinary Cancers Symposium

  8. Broad range of systemic treatment options • Adapted from NCCN v2.2019 Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf

  9. Broad range of systemic treatment options Active surveillance • Adapted from NCCN v2.2019 Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf

  10. Active surveillance in mRCC: a prospective, phase 2 trial Median surveillance time 22.2 m Median surveillance time 8.4 m Active surveillance in patients with 0–1 IMDC risk factors and two or less organs involved with metastatic disease (favourable group) compared with all other patients (unfavourable group) Rini BI, et al. Lancet Oncol 2016

  11. Broad range of systemic treatment options Active surveillance Metastasectomy • Adapted from NCCN v2.2019 Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf

  12. Meta-analysis: Outcomes following complete metastasectomy Zaid HB, et al. J Urol 2016

  13. Broad range of systemic treatment options Active surveillance Metastasectomy Cytoreductive Nephrectomy • Adapted from NCCN v2.2019 Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf

  14. Role of Cytoreductive Nephrectomy in the Cytokines era Flanigan RC, et al. N Engl J Med. 2001 Mickish GHJ, et al. Lancet 2001

  15. Role of Cytoreductive Nephrectomy in the Targeted Therapy era: Meta-anaalysis García-Perdomo HA, et al. InvestigClinUrol 2018

  16. CARMENA: OverallSurvival Méjean A, et al. N Engl J Med. 2018

  17. Bex A, et al. EurUrol 2018

  18. Broad range of systemic treatment options Active surveillance Metastasectomy Cytoreductive Nephrectomy Systemic Treatment • Adapted from NCCN v2.2019 Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf

  19. Broad range of systemic treatment options Nivolumab Everolimus Sunitinib Temsirolimus Pazopanib Active surveillance Tivozanib Metastasectomy Single agents Sorafenib Cytoreductive Nephrectomy Axitinib Cabozantinib Systemic Treatment Beva + INF Lenvatinib + Eve Nivo + Ipi Combos Atezo + Beva? Avelumab + Axi? • Adapted from NCCN v2.2019 Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf Pembro + Axi?

  20. RCC: a rapidly evolving field 1L 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … 2L

  21. RCC: a rapidly evolving field 1L INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … 2L

  22. PERCY Quattro trial: is there any better ’old’ immunotherapy for RCC? Negrier S, et al. Cancer 2005

  23. RCC: a rapidly evolving field 1L Sunitinib or Sorafenib INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … 2L

  24. First battle: Sunitinib vs Sorafenib Sunitinib vs INF Sorafenib vs INF Motzer RJ, et al. N Engl J Med 2007 Escudier B, et al. J ClinOncol 2009

  25. RCC: a rapidly evolving field 1L Sunitinib or Sorafenib Sunitinib or Temsirolimus INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … 2L

  26. The Battle for Poor Risk and Non-Clear Cell Features:Temsirolimus – Global ARCC Trial IFN + TEM TEM IFN 10.9 7.3 8.4 Hudes G, et al. N Engl J Med 2007

  27. The Battle for Poor Risk and Non-Clear Cell Features Motzer RJ, et al. J ClinOncol 2014 Armstrong AJ, et al. LancetOncol 2016 Tannir N, et al. EurUrol 2016

  28. The Battle for Poor Risk and Non-Clear Cell Features:Metaanalysis Ciccarese C, et al. Eur J Cancer 2017

  29. RCC: a rapidly evolving field 1L Sunitinib or Sorafenib Sunitinib or Temsirolimus INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … Everolimus or Sorafenib 2L

  30. RECORD-1 trial: mTOR inhibition is active in refractory RCC Motzer RJ, et al. Lancet 2008

  31. RCC: a rapidly evolving field 1L Sunitinib or Sorafenib Sunitinib or Beva + INF Sunitinib or Temsirolimus INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … Everolimus or Sorafenib 2L

  32. AVOREN and CALGB 90206 Trials: Pioneers in Doublets 8.5m 5.2m HR 0.63, 95% CI 0.52–0.75; p=0.0001 HR 0.71 (95% CI, 0.61 to 0.83; P .0001) Escudier B, et al. Lancet 2007 Rini B, et al. J ClinOncol 2008

  33. CALGB 90206 Trial Toxicity Profile (Grade 3 or 4 AEs) Rini B, et al. J ClinOncol 2008

  34. RCC: a rapidly evolving field 1L Sunitinib or Sorafenib Sunitinib or Beva + INF Sunitinib or Temsirolimus INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … Everolimus or Sorafenib 2L Axitinib or Everolimus

  35. AXIS trial: Axitinib can overcome the resistance to sunitinib Rini BI, et al. Lancet 2011

  36. RCC: a rapidly evolving field 1L Sunitinib or Sorafenib Sunitinib or Beva + INF Sunitinib or Pazopanib Sunitinib or Temsirolimus INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … Everolimus or Sorafenib 2L Axitinib or Everolimus

  37. COMPARZ Trial: Should we insist on Non-Inferiority Trials designs? Motzer RJ, et al. N Engl J Med 2013

  38. RCC: a rapidly evolving field 1L Sunitinib or Sorafenib Sunitinib or Beva + INF Sunitinib or Pazopanib Sunitinib or Temsirolimus INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … Everolimus or Sorafenib Nivolumab or Cabozantinib or Axitinib or LENEVE 2L Axitinib or Everolimus

  39. Grande E, et al. World J Clin Oncol 2017

  40. RCC: a rapidly evolving field Sunitinib or Nivo/IPI or Cabozantinib or Atezo/Bev or Pembro/Axi or Avelu/Axi or Tivozanib 1L Sunitinib or Sorafenib Sunitinib or Beva + INF Sunitinib or Pazopanib Sunitinib or Temsirolimus INF vs IL-2 or combo 2019 2007 2005 2013 2016 2017 1992 … 2011 2009 2014 2011 2018 … 2008 … Everolimus or Sorafenib Nivolumab or Cabozantinib or Axitinib or LENEVE 2L Axitinib or Everolimus

  41. Sunitinib vs The followingreferences are available from www.clinicaltrials.gov: 1. NCT01099423; 2. NCT01235962; 3. NCT02231749; 4. NCT01582672; 5. NCT00492258; 6. NCT02627963; 7. NCT01599754; 8. NCT02420821; 9. NCT02853331; 10. NCT02811861; 11. NCT02684006; 12. NCT01120249.

  42. Sunitinib vs The followingreferences are available from www.clinicaltrials.gov: 1. NCT01099423; 2. NCT01235962; 3. NCT02231749; 4. NCT01582672; 5. NCT00492258; 6. NCT02627963; 7. NCT01599754; 8. NCT02420821; 9. NCT02853331; 10. NCT02811861; 11. NCT02684006; 12. NCT01120249.

  43. ESMO 2019 Guidelines (IA recommedations) Intermediate risk Poor risk Good risk 1L Sunitinib Bevacizumab + IFN Pazopanib Tivozanib Nivolumab+ ipilimumab Nivolumab+ ipilimumab Post nivolumab + ipilimumab PostTKIs 2L VEGF TKI Nivolumab Cabozantinib Any TKI Lenvatinib + everolimus VEGF MAb + IFN- TKI + mTOR inhibitor PD-1 inhibitor (+ CTLA-4 inhibitor) • Escudier B, et al. AnnOncol 2019

  44. egrande@mdanderson.es @drenriquegrande

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