Kidney Cancer: From Basics to Immunotherapy

  • Audrey Cabral Ferreira de Oliveira
  • Fernando Nunes Galvão de OliveiraEmail author


Renal cell carcinoma (RCC) accounts for 80–85% of primary renal malignancies. The clear cell subtype is the most common and best represented in clinical trials. The detection of other histologies of renal tumors and various surgical strategies combined with the understanding of molecular biology and immunology directed to VHL-HIF-VEGF, mTOR and PD-L1 have modified the natural history of this disease and brought new dynamics to the algorithm of treatment of this disease. Our purpose is to review the biological mechanisms and present the results of important clinical trials in the area of kidney cancer.


Vascular endothelial growth factor Cancer immunotherapy Renal cell carcinoma Metastatic renal cell carcinoma Clear cell renal cell carcinoma 


  1. 1.
    Hsieh JJ, Purdue MP, Signoretti S et al (2017) Renal cell carcinoma. Nat Rev Dis Primers 3:17009CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Richie JP, Skinner DG (1981) Renal neoplasia. In: Brenner BM, Rector F (eds) The kidney, 2nd edn. WB Saunders, Philadelphia, p 2109Google Scholar
  3. 3.
    Pantuck AJ, Zisman A, Belldegrun AS (2001) The changing natural history of renal cell carcinoma. J Urol 166:1611CrossRefGoogle Scholar
  4. 4.
    SEER Stat Fact Sheets: Kidney and Renal Pelvis.
  5. 5.
    Vera Badillo FE et al (2015) Systemic therapy for non-clear cell renal cell carcinomas: a systematic review and meta-analysis. Eur Urol 67:740–749CrossRefGoogle Scholar
  6. 6.
    Porta C, Bonomi L, Lillaz B et al (2007) Renal cell carcinoma-induced immunosuppression: an immunophenotypic study of lymphocyte subpopulations and of circulating dendritic cells in patients at first diagnosis. Anticancer Res 27:165–173PubMedGoogle Scholar
  7. 7.
    Porta C, Paglino C, Imarisio I, Bonomi L (2007) Cytokine-based immunotherapy for advanced kidney cancer: past results and future perspectives in the era of molecularly targeted agents. Sci World J 7:837–849CrossRefGoogle Scholar
  8. 8.
    Beroukhim R, Brunet JP, Di Napoli A et al (2009) Patterns of gene expression and copy-number alterations in von-Hippel Lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res 69:4674–4681CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gnarra JR, Lerman MI, Zbar B, Linehan WM (1995) Genetics of renal-cell carcinoma and evidence for a critical role for von Hippel-Lindau in renal tumorigenesis. Semin Oncol 22:3–8PubMedGoogle Scholar
  10. 10.
    Gnarra JR, Tory K, Wang Y et al (1994) Mutations of the VHL tumor suppressor gene in renal carcinoma. Nat Genet 7:85–90CrossRefGoogle Scholar
  11. 11.
    Shuin T, Kondo K, Torigoe S et al (1994) Frequent somatic mutations and loss of heterozigos-ity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. Cancer Res 54:2852–2855PubMedGoogle Scholar
  12. 12.
    Herman JG, Latif F, Weng Y et al (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 91:9700–9704CrossRefGoogle Scholar
  13. 13.
    Kondo K, Yao M, Yoshida M et al (2002) Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer 34:58–68CrossRefGoogle Scholar
  14. 14.
    Brausch H, Hoeppner W, Jahning H et al (1997) Sporadic pheochromocytomas are rarely associated with germline mutations in the VHL tumor suppressor gene or the ret protooncogene. J Clin Endocrinol Metab 82:4101–4104Google Scholar
  15. 15.
    Clifford SC, Prowse AH, Affara NA et al (1998) Inactivation of the von Hippel-Lindau tumor suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma: evidence for a VHL-indipendent pathway in clear cell renal tumourigenesis. Genes Chromosomes Cancer 22:200–209CrossRefGoogle Scholar
  16. 16.
    Yu MC, Mack TM, Hanisch R, Cicioni C, Henderson BE (1986) Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. J Natl Cancer Inst 77(2):351PubMedGoogle Scholar
  17. 17.
    Shapiro JA, Williams MA, Weiss NS (1999) Body mass index and risk of renal cell carcinoma. Epidemiology 10(2):188CrossRefGoogle Scholar
  18. 18.
    Ljungberg B, Campbell SC, Choi HY et al (2011) The epidemiology of renal cell carcinoma. Eur Urol 60:615CrossRefGoogle Scholar
  19. 19.
    Gago-Dominguez M, Yuan JM, Castelao JE, Ross RK, Yu MC (1999) Regular use of analgesics is a risk factor for renal cell carcinoma. Br J Cancer 81(3):542CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Doublet JD, Peraldi MN, Gattegno B, Thibault P, Sraer JD (1997) Renal cell carcinoma of native kidneys: prospective study of 129 renal transplant patients. J Urol 158(1):42CrossRefGoogle Scholar
  21. 21.
    Hwang JJ, Uchio EM, Linehan WM, Walther MM (2003) Hereditary kidney cancer. Urol Clin North Am 30:831CrossRefGoogle Scholar
  22. 22.
    Kibel A, Iliopoulos O, DeCaprio JA, Kaelin WG Jr (1995) Binding of the von Hippel-Lindau tumor suppressor protein to elongin B and C. Science 269:1444–1446CrossRefGoogle Scholar
  23. 23.
    Maxwell PH, Wiesener MS, Chang GW et al (1999) The tumor suppressor protein VHL tar-gets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275CrossRefGoogle Scholar
  24. 24.
    Sarbassov DD, Guertin DA, Ali SM et al (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098–1101CrossRefGoogle Scholar
  25. 25.
    Fingar DC, Richardson CJ, Tee AR et al (2004) mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4EBP1/eukaryotic translation factor 4E. Mol Cell Biol 24:200–216CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Vogelzang NJ, Priest ER, Borden L (1992) Spontaneous regression of histologically proved pulmonary metastases from renal cell carcinoma: a case with 5-year followup. J Urol 148:1247CrossRefGoogle Scholar
  27. 27.
    Gleave ME, Elhilali M, Fradet Y et al (1998) Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group. N Engl J Med 338:1265CrossRefGoogle Scholar
  28. 28.
    Golimbu M, Joshi P, Sperber A et al (1986) Renal cell carcinoma: survival and prognostic factors. Urology 27:291CrossRefGoogle Scholar
  29. 29.
    Maldazys JD, deKernion JB (1986) Prognostic factors in metastatic renal carcinoma. J Urol 136:376CrossRefGoogle Scholar
  30. 30.
    Gibbons RP, Monte JE, Correa RJ Jr, Mason JT (1976) Manifestations of renal cell carcinoma. Urology 8:201CrossRefGoogle Scholar
  31. 31.
    PINALS RS, KRANE SM (1962) Medical aspects of renal carcinoma. Postgrad Med J 38:507CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Chisholm GD, Roy RR (1971) The systemic effects of malignant renal tumours. Br J Urol 43:687CrossRefGoogle Scholar
  33. 33.
    Da Silva JL, Lacombe C, Bruneval P et al (1990) Tumor cells are the site of erythropoietin synthesis in human renal cancers associated with polycythemia. Blood 75:577CrossRefGoogle Scholar
  34. 34.
    Gold PJ, Fefer A, Thompson JA (1996) Paraneoplastic manifestations of renal cell carcinoma. Semin Urol Oncol 14:216PubMedGoogle Scholar
  35. 35.
    Weissglas M, Schamhart D, Löwik C et al (1995) Hypercalcemia and cosecretion of interleukin-6 and parathyroid hormone related peptide by a human renal cell carcinoma implanted into nude mice. J Urol 153:854CrossRefGoogle Scholar
  36. 36.
    Pras M, Franklin EC, Shibolet S, Frangione B (1982) Amyloidosis associated with renal cell carcinoma of the AA type. Am J Med 73:426CrossRefGoogle Scholar
  37. 37.
    Utz DC, Warren MM, Gregg JA et al (1970) Reversible hepatic dysfunction associated with hypernephroma. Mayo Clin Proc 45:161PubMedGoogle Scholar
  38. 38.
    Johnson CD, Dunnick NR, Cohan RH, Illescas FF (1987) Renal adenocarcinoma: CT staging of 100 tumors. AJR Am J Roentgenol 148:59CrossRefGoogle Scholar
  39. 39.
    Koga S et al (2001) The diagnostic value of bone scan in patients with renal cell carcinoma. J Urol 166(6):2126–2128CrossRefGoogle Scholar
  40. 40.
    Semelka RC et al (1993) Renal cancer staging: comparison of contrast-enhanced CT and gadolinium-enhanced fat-suppressed spin-echo and gradient-echo MR imaging. J Magn Reson Imaging 3(4):597–602CrossRefGoogle Scholar
  41. 41.
    Majhail NS et al (2003) F-18 fluorodeoxyglucose positron emission tomography in the evaluation of distant metastases from renal cell carcinoma. J Clin Oncol 21(21):3995–4000CrossRefGoogle Scholar
  42. 42.
    Patil S et al (2011) Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol 22:295–300CrossRefGoogle Scholar
  43. 43.
    Heng DYC 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 27:5794CrossRefGoogle Scholar
  44. 44.
    Rini BI, McKiernan JM, Chang SS et al (2017) Kidney. In: Amin MB (ed) AJCC cancer staging manual, 8th edn. Springer, New York, p 739Google Scholar
  45. 45.
    Aubert S, Zini L, Delomez J et al (2005) Cystic renal cell carcinomas in adults. Is preoperative recognition of multilocular cystic renal cell carcinoma possible? J Urol 174:2115CrossRefGoogle Scholar
  46. 46.
    Bielsa O, Lloreta J, Gelabert-Mas A (1998) Cystic renal cell carcinoma: pathological features, survival and implications for treatment. Br J Urol 82:16CrossRefGoogle Scholar
  47. 47.
    Cancer Genome Atlas Research Network, Linehan WM, Spellman PT et al (2016) Comprehensive molecular characterization of papillary renal-cell carcinoma. N Engl J Med 374:135CrossRefGoogle Scholar
  48. 48.
    Thoenes W, Störkel S, Rumpelt HJ et al (1988) Chromophobe cell renal carcinoma and its variants–a report on 32 cases. J Pathol 155:277CrossRefGoogle Scholar
  49. 49.
    Störkel S, Steart PV, Drenckhahn D, Thoenes W (1989) The human chromophobe cell renal carcinoma: its probable relation to intercalated cells of the collecting duct. Virchows Arch B Cell Pathol Incl Mol Pathol 56:237CrossRefGoogle Scholar
  50. 50.
    Speicher MR, Schoell B, du Manoir S et al (1994) Specific loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe renal cell carcinomas revealed by comparative genomic hybridization. Am J Pathol 145:356PubMedPubMedCentralGoogle Scholar
  51. 51.
    Orsola A, Trias I, Raventós CX et al (2005) Renal collecting (Bellini) duct carcinoma displays similar characteristics to upper tract urothelial cell carcinoma. Urology 65:49CrossRefGoogle Scholar
  52. 52.
    Swartz MA, Karth J, Schneider DT et al (2002) Renal medullary carcinoma: clinical, pathologic, immunohistochemical, and genetic analysis with pathogenetic implications. Urology 60:1083CrossRefGoogle Scholar
  53. 53.
    Strouse JJ, Spevak M, Mack AK et al (2005) Significant responses to platinum-based chemotherapy in renal medullary carcinoma. Pediatr Blood Cancer 44:407CrossRefGoogle Scholar
  54. 54.
    Campbell SC, Novick AC, Belldegrun A et al (2009) Guideline for management of the clinical T1 renal mass. J Urol 182:1271CrossRefGoogle Scholar
  55. 55.
    Ravaud A, Motzer RJ, Pandha HS et al (2016) Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med 375:2246CrossRefGoogle Scholar
  56. 56.
    Robson CJ (1963) Radical nephrectomy for renal cell carcinoma. J Urol 89:37CrossRefGoogle Scholar
  57. 57.
    Colombo JR Jr, Haber GP, Jelovsek JE et al (2008) Seven years after laparoscopic radical nephrectomy: oncologic and renal functional outcomes. Urology 71:1149CrossRefGoogle Scholar
  58. 58.
    Tan H-J, Norton EC, Ye Z et al (2012) Long-term survival following partial vs radical nephrectomy among older patients with early-stage kidney cancer. JAMA 307:1629CrossRefGoogle Scholar
  59. 59.
    Carini M, Minervini A, Masieri L et al (2006) Simple enucleation for the treatment of PT1a renal cell carcinoma: our 20-year experience. Eur Urol 50:1263CrossRefGoogle Scholar
  60. 60.
    Kunkle DA, Uzzo RG (2008) Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer 113:2671CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Flanigan RC, Salmon SE, Blumenstein BA et al (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345:1655CrossRefGoogle Scholar
  62. 62.
    Mickisch GH, Garin A, van Poppel H et al (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358:966CrossRefGoogle Scholar
  63. 63.
    Mejean A, Ravaud A, Thezenas S et al (2018) Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med 379(5):417–427CrossRefGoogle Scholar
  64. 64.
    Middleton AW Jr (1980) Indications for and results of nephrectomy for metastatic renal cell carcinoma. Urol Clin North Am 7:711PubMedGoogle Scholar
  65. 65.
    Alt AL, Boorjian SA, Lohse CM et al (2011) Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer 117:2873CrossRefGoogle Scholar
  66. 66.
    Lin PP, Mirza AN, Lewis VO et al (2007) Patient survival after surgery for osseous metastases from renal cell carcinoma. J Bone Joint Surg Am 89:1794CrossRefGoogle Scholar
  67. 67.
    Lee DS, White DE, Hurst R et al (1998) Patterns of relapse and response to retreatment in patients with metastatic melanoma or renal cell carcinoma who responded to interleukin-2-based immunotherapy. Cancer J Sci Am 4:86PubMedGoogle Scholar
  68. 68.
    Haas NB, Manola J, Uzzo RG et al (2016) Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet 387:2008–2016CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    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 28:1061CrossRefGoogle Scholar
  70. 70.
    Motzer RJ, Haas NB, Donskov F et al (2017) Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma. J Clin Oncol 35:3916CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Motzer RJ, Hutson TE, Tomczak P et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Motzer RJ, Hutson TE, McCann L et al (2014) Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med 370:1769CrossRefGoogle Scholar
  73. 73.
    Escudier B, Porta C, Bono P et al (2014) 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 32:1412CrossRefGoogle Scholar
  74. 74.
    Choueiri TK, Escudier B, Powles T et al (2015) Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1814CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    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 35:591CrossRefGoogle Scholar
  76. 76.
    Hutson TE, Lesovoy V, Al-Shukri S et al (2013) Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol 14:1287CrossRefGoogle Scholar
  77. 77.
    Bracarda S, Bellmunt J, Melichar B et al (2011) Overall survival in patients with metastatic renal cell carcinoma initially treated with bevacizumab plus interferon-α2a and subsequent therapy with tyrosine kinase inhibitors: a retrospective analysis of the phase III AVOREN trial. BJU Int 107:214CrossRefGoogle Scholar
  78. 78.
    Rini BI, Halabi S, Rosenberg JE et al (2010) 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 28:2137CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271CrossRefGoogle Scholar
  80. 80.
    Motzer RJ, Barrios CH, Kim TM et al (2013) Record-3: phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) versus first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol 31(suppl):abstr 4504Google Scholar
  81. 81.
    Knox JJ, Barrios CH, Kim TM, Cosgriff T, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page RD, Beck JT, Cheung F, Yadav S, Patel P, Geoffrois L, Niolat J, Berkowitz N, Marker M, Chen D, Motzer RJ (2017) Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC. Ann Oncol 28(6):1339–1345CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Escudier B, Motzer RJ, Sharma P et al (2017) Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025. Eur Urol 72:368CrossRefGoogle Scholar
  83. 83.
    Motzer RJ, Tannir NM, McDermott DF et al (2018) Nivolumab plus Ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378:1277CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Motzer R, Powles T, Atkins M et al IMmotion151: a randomized phase III study of atezolizumab plus bevacizumab vs sunitinib in untreated metastatic renal cell carcinoma. In: Presented at the 2018 genitourinary cancers symposiumGoogle Scholar
  85. 85.
    Belldegrun AS, Klatte T, Shuch B et al (2008) Cancer-specific survival outcomes among patients treated during the cytokine era of kidney cancer (1989–2005): a benchmark for emerging targeted cancer therapies. Cancer 113:2457CrossRefGoogle Scholar
  86. 86.
    Armstrong AJ, Halabi S, Eisen T et al (2016) Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol 17:378–388CrossRefGoogle Scholar
  87. 87.
    Escudier B, Molinie V, Bracarda S et al (2016) Open-label phase 2 trial of first-line everolimus monotherapy in patients with papillary metastatic renal cell carcinoma: RAPTOR final analysis. Eur J Cancer 69:226CrossRefGoogle Scholar
  88. 88.
    Srinivasan R et al (2014) Mechanism based targeted therapy for hereditary leimyomatosis and renal cell cancer and sporadic papillary renal cell carcinoma: interim results from a phase 2 study of bevacizumab and erlotinib (abstract 5). EORTC-NCI-AACR symposium on molecular targets and cancer therapeuticsGoogle Scholar
  89. 89.
    Michaelson MD, McDermott DF, Atkins MB et al (2013) Combination of antiangiogenic therapy and cytotoxic chemotherapy for sarcomatoid renal cell carcinoma. ASCO Meet Abstr 31:4512Google Scholar
  90. 90.
    Golshayan AR, George S, Heng DY et al (2009) Metastatic sarcomatoid renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. J Clin Oncol 27:235CrossRefGoogle Scholar
  91. 91.
    Choueiri TK, Plantade A, Elson P et al (2008) Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol 26:127CrossRefGoogle Scholar
  92. 92.
    Srigley JR, Moch Heble JN (2004) Carcinoma of the collecting ducts of Bellini. World Health Organization Classification of Tumors Pathology & Genetics: Tumors of the Urinary System and Male Genital Organs. IARC, Lyon, pp 33–34Google Scholar
  93. 93.
    Oudard S, Banu E, Vieillefond A et al (2007) Prospective multicenter phase II study of gemcitabine plus platinum salt for metastatic collecting duct carcinoma: results of a GETUG (Groupe d’Etudes des Tumeurs Uro-Génitales) study. J Urol 177:1698CrossRefGoogle Scholar
  94. 94.
    Procopio G, Testa I, Iacovelli R, Grassi P, Verzoni E, Garanzini E, Colecchia M, Torelli T, De Braud F (2014) Treatment of collecting duct carcinoma: current status and future perspectives. Anticancer Res 34(2):1027–1030PubMedGoogle Scholar
  95. 95.
    Hakimi AA, Koi PT, Milhoua PM et al (2007) Renal medullary carcinoma: the Bronx experience. Urology 70:878CrossRefGoogle Scholar
  96. 96.
    Carlos MI et al (2016) Medullary renal cell carcinoma (RCC): genomics and treatment outcomes. J Clin Oncol 34:Abstr 4556Google Scholar
  97. 97.
    Choueiri TK, Lim ZD, Hirsch MS et al (2010) Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma. Cancer 116:5219CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Koshkin VS, Barata PC, Zhang T et al (2018) Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma. J Immunother Cancer 6:9CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Bristol-Myers Squibb. A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 9ER). Accessed July 2018
  100. 100.
    Motzer R et al (2018) IMmotion151: a randomized phase III study of Atezolizumab plus bevacizumab vs sunitinib in untreated metastatic renal cell carcinoma (mRCC). J Clin Oncol 36(6_suppl):578–578Google Scholar
  101. 101.
    Amin A, Dudek AZ, Logan TF et al (2015) Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): phase 2 study results. J Immunother Cancer 3:14CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Atkins MB, Plimack ER, Puzanov I et al (2016) Axitinib in combination with pembrolizumab in patients (pts) with advanced renal cell carcinoma (aRCC): preliminary safety and efficacy results. Ann Oncol 6:266, abstract 773PDGoogle Scholar
  103. 103.
    Merck Sharp & Dohme Corp Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma (MK-3475-426/KEYNOTE-426). Accessed July 2018
  104. 104.
    Argos Therapeutics. Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma (ADAPT). Accessed July 2018
  105. 105.
    Pfizer. A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101). Accessed July 2018
  106. 106.
    Merck Sharp & Dohme Corp. Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564). Accessed July 2018
  107. 107.
    Eisai Inc. Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma (CLEAR). Accessed July 2018
  108. 108.
    Hoffmann-La Roche. A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy (IMmotion010). Accessed July 2018
  109. 109.
    Bristol-Myers Squibb. A Study Comparing the Combination of Nivolumab and Ipilimumab Versus Placebo in Participants With Localized Renal Cell Carcinoma (CheckMate 914). Accessed July 2018

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Audrey Cabral Ferreira de Oliveira
    • 1
  • Fernando Nunes Galvão de Oliveira
    • 1
    Email author
  1. 1.Medical OncologyClion – Clínica de OncologiaSalvadorBrazil

Personalised recommendations