Checkpoint Inhibitors for the Treatment of Renal Cell Carcinoma

Current Treatment Options in Oncology

Volumn 18, Issue 1, 2017, Pages

  Ghatalia, Pooja ^a   Zibelman, Matthew ^a   Geynisman, Daniel M ^a   Plimack, Elizabeth R ^a  

^a FOX CHASE CANCER CENTER   (United States)

Author keywords

Cytotoxic T lymphocyte associated protein 4; Immune checkpoint blockade; Immunotherapy; Programmed death 1; Renal cell carcinoma; VEGF

Indexed keywords

4 AMINO N (3 CHLORO 4 FLUOROPHENYL) N' HYDROXY 1,2,5 OXADIAZOLE 3 CARBOXIMIDAMIDE; AFLIBERCEPT; AM 0010; ANTINEOPLASTIC AGENT; ATEZOLIZUMAB; AVELUMAB; AXITINIB; BEVACIZUMAB; CABOZANTINIB; CB 839; CPI 444; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DURVALUMAB; ENOBLITUZUMAB; FPA 008; IPILIMUMAB; LENVATINIB; MOXR 0916; NIVOLUMAB; PAZOPANIB; PEGINTERFERON ALPHA2B; PEMBROLIZUMAB; SUNITINIB; TICILIMUMAB; TUCIDINOSTAT; UNCLASSIFIED DRUG; UTOMILUMAB; VARLILUMAB; VASCULOTROPIN INHIBITOR; VORINOSTAT; IMMUNOLOGIC FACTOR; MONOCLONAL ANTIBODY; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; TUMOR MARKER;

CLINICAL TRIAL (TOPIC); DRUG EFFECT; DRUG EFFICACY; HUMAN; KIDNEY CARCINOMA; PATIENT SAFETY; PATIENT SELECTION; REVIEW; TREATMENT OUTCOME; TREATMENT RESPONSE; ANTAGONISTS AND INHIBITORS; CARCINOMA, RENAL CELL; DRUG EFFECTS; IMMUNOLOGY; IMMUNOMODULATION; KIDNEY NEOPLASMS; METABOLISM; MOLECULARLY TARGETED THERAPY; T LYMPHOCYTE;

ANTIBODIES, MONOCLONAL; ANTIGENS, CD274; ANTINEOPLASTIC AGENTS; BIOMARKERS, TUMOR; CARCINOMA, RENAL CELL; CLINICAL TRIALS AS TOPIC; CTLA-4 ANTIGEN; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOMODULATION; KIDNEY NEOPLASMS; MOLECULAR TARGETED THERAPY; PATIENT SELECTION; PROGRAMMED CELL DEATH 1 RECEPTOR; T-LYMPHOCYTES; TREATMENT OUTCOME;

EID: 85013188059     PISSN: 15272729     EISSN: 15346277     Source Type: Journal    
DOI: 10.1007/s11864-017-0458-0     Document Type: Review

References (53)

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.
2. SEER Stat Fact Sheets: Kidney and Renal Pelvis Cancer. Available from: http://seer.cancer.gov/statfacts/html/kidrp.html.
3. Fisher RI, Rosenberg SA, Fyfe G. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000;6(Suppl 1):S55–7.
4. Fyfe G, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13(3):688–96.
5. Rini BI, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26(33):5422–8.
6. Escudier B, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370(9605):2103–11.
7. Motzer RJ, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369(8):722–31.
8. Motzer RJ, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24.
9. Sternberg CN, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061–8.
10. • Motzer RJ, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13. This phase III randomized trial showed superiority of nivolumab compared to everolimus. Based on these results, nivolumab is now a standard second-line therapy for metastatic renal cell carcinoma.
11. Hammers H. 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. ESMO 2016 meeting. 1062P.
12. McDermott D. A phase 1/2 study to assess the safety and efficacy of pazopanib and pembrolizumab in patients with advanced renal cell carcinoma. European Cancer Congress 2015; Vienna, Austria.
13. Yang JC, et al. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother. 2007;30(8):825–30.
14. • Choueiri TK, et al. Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma. Clin Cancer Res 2016: p 5461–71. Pre-treatment and on- treatment tissue samples were prospectively collected to investigate mechanism of action of nivoulmab in RCC as part of this phase II trial. Analysis of these samples revealed evidence of immunomodulatory activity with increases in tumor associated lymphocytes and transcriptional changes in IFN gamma-stimulated genes after treatment with nivolumab.
15. Motzer RJ, et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015;33(13):1430–7.
16. Dong H, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.
17. Fife BT, et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol. 2009;10(11):1185–92.
18. Rudd CE. The reverse stop-signal model for CTLA4 function. Nat Rev Immunol. 2008;8(2):153–60.
19. Ko JS, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15(6):2148–57.
20. Kusmartsev S, Gabrilovich DI. Role of immature myeloid cells in mechanisms of immune evasion in cancer. Cancer Immunol Immunother. 2006;55(3):237–45.
21. Du Four S, et al. Axitinib increases the infiltration of immune cells and reduces the suppressive capacity of monocytic MDSCs in an intracranial mouse melanoma model. Oncoimmunology. 2015;4(4):e998107.
22. Terme M, et al. Modulation of immunity by antiangiogenic molecules in cancer. Clin Dev Immunol. 2012;2012:492920.
23. Amin A, et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC). J Clin Oncol (Meeting Abstracts). 2014;32(15_suppl):5010.
24. Choueiri TK, 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(7):917–27.
25. Apolo A, Mortazavi A, Stein M. A phase I study of cabozantinib plus nivolumab (CaboNivo) in patients (pts) refractory metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors. 2016. Ann Oncol 27 (suppl 6).
26. Flanigan RC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001;345(23):1655–9.
27. Mickisch G, et al. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001;358(9286):966–70.
28. Patnaik A, et al. Phase I study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res. 2015;21(19):4286–93.
29. Atkins M. Axitinib in combination with pembrolizumab in patients (pts) with advanced renal cell carcinoma (aRCC): preliminary safety and efficacy results. ESMO 2016 meeting. 773PD.
30. Infante, J.R., et al. A phase I, multicenter, open-label, first-in-human study to evaluate MEDI0680, an anti-programmed cell death-1 antibody, in patients with advanced malignancies. in ASCO Annual Meeting Proceedings. 2015.
31. McDermott DF, 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. 2016;34(8):833–42.
32. Wallin JJ, et al. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun. 2016;7:12624.
33. Sznol M. Phase Ib evaluation of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) in patients (pts) with metastatic renal cell carcinoma (mRCC). J Clin Oncol 33, 2015 (suppl 7; abstr 410).
34. Krummel MF, Allison JP. Pillars article: CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182:459–65. J Immunol, 2011. 187(7): p. 3459-65
35. Schwartz RH. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992;71(7):1065–8.
36. O’Day SJ, Hamid O, Urba WJ. Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4). Cancer. 2007;110(12):2614–27.
37. Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(13):1270–1.
38. Rini BI, et al. Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma. Cancer. 2011;117(4):758–67.
39. Robert C, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.
40. Grosso JF, et al. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest. 2007;117(11):3383–92.
41. Brignone C, et al. A phase I pharmacokinetic and biological correlative study of IMP321, a novel MHC class II agonist, in patients with advanced renal cell carcinoma. Clin Cancer Res. 2009;15(19):6225–31.
42. Linch SN, McNamara MJ, Redmond WL. OX40 agonists and combination immunotherapy: putting the pedal to the metal. Front Oncol. 2015;5:34.
43. Tolcher A. Phase Ib study of PF-05082566 in combination with pembrolizumab in patients with advanced solid tumors. J Clin Oncol 34, 2016 (suppl; abstr 3002).
44. Infante J. A phase Ib dose escalation study of the OX40 agonist MOXR0916 and the PD-L1 inhibitor atezolizumab in patients with advanced solid tumors. J Clin Oncol 34, 2016 (suppl; abstr 101).
45. Liu X, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010;115(17):3520–30.
46. Gangadhar T. Epacadostat plus pembrolizumab in patients with advanced melanoma and select solid tumors: updated phase 1 results from ECHO-202/KEYNOTE-037. 2016: Ann Oncol 27 (6): abstract 1110PD.
47. Thompson RH, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006;66(7):3381–5.
48. Mahoney K, Kotecha R, CM. Association of higher PD-L1 expression in tumor cells of metastatic ccRCC lesions with worse overall survival. J Clin Oncol 34, 2016 (suppl; abstr e23221).
49. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847–56.
50. Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24(2):207–12.
51. Chiou VL, Burotto M. Pseudoprogression and immune-related response in solid tumors. J Clin Oncol. 2015;33(31):3541–3.
52. Wolchok JD, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412–20.
53. Atkinson V. Complete responders to anti-PD1 antibodies. What happens when we stop? ESMO 2016 meeting. 1116P.