Nivolumab in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience.
Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α). Strategies of tumor immune evasion include T-cell suppression by negative signals deriving from the interaction between programmed death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells. Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus reversing T-cell suppression and activating antitumor responses. The aim of this review is to summarize the safety and efficacy data of nivolumab in mRCC. Objective responses and safety profile of single-agent nivolumab are favorable in both previously treated and treatment-naïve mRCC patients. Despite toxic effects, combination therapies with nivolumab have shown promising results, indicating a potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to-patient basis represents a major challenge for the future.
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Alessia
A
Mennitto
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Paolo
P
Grassi
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Raffaele
R
Ratta
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Elena
E
Verzoni
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Michele
M
Prisciandaro
Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
Giuseppe
G
Procopio
immunotherapy; nivolumab; programmed death-1; renal cell carcinoma
Pharmacol Ther. 2015 Apr;148:132-53
25476108
Clin Cancer Res. 2007 Mar 15;13(6):1757-61
17363529
Expert Rev Anticancer Ther. 2016;16(2):133-5
26654053
N Engl J Med. 2012 Jun 28;366(26):2443-54
22658127
Nature. 2014 Nov 27;515(7528):568-71
25428505
J Urol. 1977 Oct;118(4):538-42
916044
Cancer Res. 2010 May 1;70(9):3526-36
20406969
Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):716s-720s
17255299
Lancet. 2016 Feb 27;387(10021):894-906
26318520
J Clin Oncol. 2010 Jul 1;28(19):3167-75
20516446
N Engl J Med. 2015 Nov 5;373(19):1803-13
26406148
J Clin Oncol. 2012 Feb 10;30(5):482-7
22231040
Clin Cancer Res. 2013 Jan 15;19(2):462-8
23169436
Annu Rev Immunol. 2008;26:677-704
18173375
Expert Rev Anticancer Ther. 2012 Dec;12(12):1571-7
23181412
Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12293-7
12218188
Clin Cancer Res. 2014 Oct 1;20(19):5064-74
24714771
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-9
15569934
Clin Cancer Res. 2009 Mar 15;15(6):2148-57
19276286
Cancer. 2005 Nov 15;104(10):2084-91
16208700
Eur Urol. 2016 Sep;70(3):e72-4
26947604
Curr Opin Immunol. 2007 Jun;19(3):309-14
17433872
Cancer Immunol Res. 2014 Sep;2(9):846-56
24872026
Oncology. 2013;84(1):39-42
23076302
Clin Cancer Res. 2015 Mar 1;21(5):1071-7
25538263
N Engl J Med. 2007 Jan 11;356(2):115-24
17215529
Ann Oncol. 2012 Oct;23 Suppl 7:vii65-71
22997456
J Clin Oncol. 2015 May 1;33(13):1430-7
25452452
J Cancer. 2014 Jan 24;5(3):166-72
24563671
Oncoimmunology. 2012 Nov 1;1(8):1451-1453
23243626
Anticancer Res. 2007 Jan-Feb;27(1A):165-73
17352228
Cancer Immunol Res. 2014 Apr;2(4):320-31
24764579
Int Immunol. 2010 Aug;22(8):651-60
20587542
N Engl J Med. 2001 Dec 6;345(23):1655-9
11759643
Clin Cancer Res. 2013 Sep 15;19(18):4917-24
23868869
J Clin Oncol. 2017 Dec 1;35(34):3851-3858
28678668