Immune checkpoint inhibitors in advanced renal cell carcinoma: experience to date and future directions

Annals of Oncology

Volumn 28, Issue 7, 2017, Pages 1484-1494

  Atkins, M B ^a   Clark, J I ^b   Quinn, D I ^c  

^a GEORGETOWN UNIVERSITY   (United States)

^b LOYOLA UNIVERSITY CHICAGO   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

anti CTLA 4; anti PD 1 PD L1; immune checkpoint inhibitors; overall survival; renal cell carcinoma

Indexed keywords

ANTINEOPLASTIC AGENT; CTLA4 PROTEIN, HUMAN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; PDCD1 PROTEIN, HUMAN; PROGRAMMED DEATH 1 RECEPTOR;

ANIMAL; ANTAGONISTS AND INHIBITORS; FORECASTING; HUMAN; IMMUNOLOGY; IMMUNOTHERAPY; KIDNEY TUMOR; MASS COMMUNICATION; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOLOGY; PROCEDURES; RENAL CELL CARCINOMA; TREATMENT OUTCOME; TRENDS;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, RENAL CELL; CTLA-4 ANTIGEN; DIFFUSION OF INNOVATION; FORECASTING; HUMANS; IMMUNOTHERAPY; KIDNEY NEOPLASMS; MOLECULAR TARGETED THERAPY; PROGRAMMED CELL DEATH 1 RECEPTOR; TREATMENT OUTCOME;

EID: 85029665479     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdx151     Document Type: Review

References (63)

1. Ferlay, J., Soerjomataram, I., Dikshit, R., et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136 (2015), E359–E386.
2. Siegel, R.L., Miller, K.D., Jemal, A., Cancer statistics, 2016. CA Cancer J Clin 66 (2016), 7–30.
3. Fisher, R., Gore, M., Larkin, J., Current and future systemic treatments for renal cell carcinoma. Semin Cancer Biol 23 (2013), 38–45.
4. Hudes, G.R., Carducci, M.A., Choueiri, T.K., et al. NCCN Task Force report: optimizing treatment of advanced renal cell carcinoma with molecular targeted therapy. J Natl Compr Canc Netw 9 (2011), S1–S29.
5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Kidney Cancer V.2.2017. National Comprehensive Cancer Network, Inc. 2017. All rights reserved. 22 February 2017, date last accessed.
6. Escudier, B., Porta, C., Schmidinger, M., et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 27 (2016), v58–v68.
7. Choueiri, T.K., Escudier, B., Powles, T., et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373 (2015), 1814–1823.
8. Drugs@FDA database.Cabozantinib. US Food and Drug Administration Website. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (11 July 2016, date last accessed).
9. Motzer, R.J., Hutson, T.E., Glen, H., et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol 16 (2015), 1473–1482.
10. Drugs@FDA database. Lenvatinib. US Food and Drug Administration Website. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (11 July 2016, date last accessed).
11. Rini, B.I., Atkins, MB., Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol 10 (2009), 992–1000.
12. Drugs@FDA database.Nivolumab. US Food and Drug Administration Website. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (11 July 2016, date last accessed).
13. Opdivo [Summary of Product Characteristics]. Uxbridge, UK: Bristol-Myers Squibb Pharma EEIG 2015.
14. Motzer, R.J., Escudier, B., McDermott, D.F., et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373 (2015), 1803–1813.
15. Pardoll, DM., The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12 (2012), 252–264.
16. Brahmer, J.R., Hammers, H., Lipson, EJ., Nivolumab: targeting PD-1 to bolster antitumor immunity. Future Oncol 11 (2015), 1307–1326.
17. Medina, P.J., Adams, VR., PD-1 pathway inhibitors: immuno-oncology agents for restoring antitumor immune responses. Pharmacotherapy 36 (2016), 317–334.
18. Thompson, R.H., Gillett, M.D., Cheville, J.C., et al. Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A 101 (2004), 17174–17179.
19. Thompson, R.H., Dong, H., Lohse, C.M., et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res 13 (2007), 1757–1761.
20. Raman, R., Vaena, D., Immunotherapy in metastatic renal cell carcinoma: a comprehensive review. Biomed Res Int, 2015, 2015, 367354.
21. Kreamer, KM., Immune checkpoint blockade: a new paradigm in treating advanced cancer. J Adv Pract Oncol 5 (2014), 418–431.
22. Hodi, F.S., O'Day, S.J., McDermott, D.F., et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363 (2010), 711–723.
23. Robert, C., Thomas, L., Bondarenko, I., et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364 (2011), 2517–2526.
24. Opdivo (Nivolumab) Injection [Prescribing Information]. Princeton, NJ: Bristol-Myers Squibb Co. 2016.
25. Robert, C., Schachter, J., Long, G.V., et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372 (2015), 2521–2532.
26. Keytruda (Pembrolizumab) [Prescribing Information]. Whitehouse Station, NJ: Merck Sharp & Dohme 2015.
27. McDermott, D.F., Sosman, J.A., Sznol, M., et al. Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol 34 (2016), 833–842.
28. Tecentriq (Atezolizumab) Injection [Prescribing Information]. South San Francisco, CA: Genentech 2016.
29. Yang, J.C., Hughes, M., Kammula, U., et al. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother 30 (2007), 825–830.
30. Topalian, S.L., Hodi, F.S., Brahmer, J.R., et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366 (2012), 2443–2454.
31. McDermott, D.F., Drake, C.G., Sznol, M., et al. Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. J Clin Oncol 33 (2015), 2013–2020.
32. McDermott, D.F., Motzer, R.J., Atkins, M.B., et al. Long-term overall survival (OS) with nivolumab in previously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies [ASCO oral presentation]. J Clin Oncol, 34, 2016, 4507.
33. Motzer, R.J., Rini, B.I., McDermott, D.F., et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol 33 (2015), 1430–1437.
34. Cella, D., Yount, S., Brucker, P.S., et al. Development and validation of a scale to measure disease-related symptoms of kidney cancer. Value Health 10 (2007), 285–293.
35. Cella, D., Grünwald, V., Nathan, P., et al. Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial. Lancet Oncol 17 (2016), 994–1003.
36. Naidoo, J., Page, D.B., Li, B.T., et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol 26 (2015), 2375–2391.
37. Wolchok, J.D., Hoos, A., O'Day, S., et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15 (2009), 7412–7420.
38. Chiou, V.L., Burotto, M., Pseudoprogression and immune-related response in solid tumors. J Clin Oncol 33 (2015), 3541–3543.
39. George, S., Motzer, R.J., Hammers, H.J., et al. Safety and efficacy of nivolumab in patients with metastatic renal cell carcinoma treated beyond progression: a subgroup analysis of a randomized clinical trial. JAMA Oncol 2 (2016), 1179–1186.
40. Escudier, B., Motzer, R.J., Sharma, P., et al. Treatment beyond progression with nivolumab (nivo) in patients (pts) with advanced renal cell carcinoma (aRCC) in the phase III CheckMate 025 study. J Clin Oncol, 34(15), 2016, 4509.
41. Weinstock, C., Maher, V.E., Zhang, L., et al. FDA analysis of treatment beyond disease progression disease (PD) in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab vs. everolimus. J Clin Oncol, 34(15), 2016, 4508.
42. Parekh, H., Rini, BI., Emerging therapeutic approaches in renal cell carcinoma. Expert Rev Anticancer Ther 15 (2015), 1305–1314.
43. Schmid, P., Hedge, P.S., Zou, W., et al. Association of PDL2 expression in human tumors with atezolizumab activity. J Clin Oncol, 34(15), 2016, 11506.
44. Choueiri, T.K., Figueroa, D.J., Fay, A.P., et al. Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib: results from COMPARZ, a randomized controlled trial. Clin Cancer Res 21 (2015), 1071–1077.
45. Ascierto, M.L., McMiller, T.L., Berger, A.E., et al. The intratumoral balance between metabolic and immunologic gene expression is associated with anti-PD-1 response in patients with renal cell carcinoma. Cancer Immunol Res 4 (2016), 726–733.
46. Choueiri, T.K., Fishman, M.N., Escudier, B., et al. Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma. Clin Cancer Res 22 (2016), 5461–5471.
47. Motzer, R.J., Sharma, P., McDermott, D.F., et al. CheckMate 025 phase III trial: Outcomes by key baseline factors and prior therapy for nivolumab (NIVO) vs everolimus (EVE) in advanced renal cell carcinoma (RCC). J Clin Oncol, 34(2), 2016, 498.
48. Motzer, R.J., Escudier, B., Choueiri, TK., Treatment of advanced renal-cell carcinoma. N Engl J Med 374 (2016), 889–890.
49. Harshman, L.C., Drake, C.G., Choueiri, TK., PD-1 blockade in renal cell carcinoma: to equilibrium and beyond. Cancer Immunol Res 2 (2014), 1132–1141.
50. Quinn, D.I., Lara, P.N. Jr, Renal-cell cancer-targeting an immune checkpoint or multiple kinases. N Engl J Med 373 (2015), 1872–1874.
51. Choueiri, T.K., Escudier, B., Powles, T., et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol 17 (2016), 917–927.
52. Aoun, F., Kourie, H.R., Sideris, S., et al. Checkpoint inhibitors in bladder and renal cancers: results and perspectives. Immunotherapy 7 (2015), 1259–1271.
53. Wolchok, J.D., Kluger, H., Callahan, M.K., et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369 (2013), 122–133.
54. Hammers, H., Plimack, E.R., Infante, J.R., et al. Updated results from a phase I study of nivolumab (Nivo) in combination with ipilimumab (Ipi) in metastatic renal cell carcinoma (mRCC): the CheckMate 016 study. Ann Oncol, 27(6), 2016, 2062P.
55. Hughes, P.E., Caenepeel, S., Wu, LC., Targeted therapy and checkpoint immunotherapy combinations for the treatment of cancer. Trends Immunol 37 (2016), 462–476.
56. Amin, A., Plimack, E.R., Infante, J.R., et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib (S) or pazopanib (P) in patients (pts) with metastatic renal cell carcinoma (mRCC). Ann Oncol, 25(4), 2014, 1052PD.
57. McDermott, D.F., Infacte, J.R., Chowdhury, S., et al. A phase 1/2 study to assess the safety and efficacy of pazopanib and pembrolizumab in patients with advanced renal cell carcinoma. Eur J Cancer, 51(3), 2015, 2622.
58. Atkins, M.B., Plimack, E.R., Puzanov, I., et al. Axitinib in combination with pembrolizumab in patients (pts) with advanced renal cell carcinoma (aRCC): preliminary safety and efficacy results. J Immunother Cancer, 3(2), 2016, P353.
59. Larkin, J., Rini, B.I., Nathan, P., et al. Phase 1b dose-finding study of avelumab (anti-PD-L1) + axitinib in treatment-naïve patients with advanced renal cell carcinoma. Ann Oncol, 27(6), 2016, 775PD.
60. Wallin, J.J., Bendell, J.C., Funke, R., et al. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun, 7, 2016, 12624.
61. Atkins, M.B., Gupta, S., Choueiri, T.K., et al. Phase Ib dose-finding study of axitinib plus pembrolizumab in treatment-naïve patients with advanced renal cell carcinoma. J Immunother Cancer, 3(2), 2015, P353.
62. Weinstock, M., McDermott, D., Targeting PD-1/PD-L1 in the treatment of metastatic renal cell carcinoma. Ther Adv Urol 7 (2015), 365–377.
63. Larkin, J., Chiarion-Sileni, V., Gonzalez, R., et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373 (2015), 23–34.