#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Immunotherapy of Renal Cell Carcinoma


Authors: A. Poprach 1;  R. Lakomý 1;  T. Büchler 2
Authors‘ workplace: Klinika komplexní onkologické péče a Masarykův onkologický ústav, Brno 1;  Onkologická klinika 1. LF UK a Thomayerova nemocnice, Praha 2
Published in: Klin Onkol 2017; 30(Supplementum3): 55-61
Category: Review
doi: https://doi.org/10.14735/amko20173S55

Overview

Treatment of renal cell carcinoma is still palliative. Targeted therapy increases response rates and prolongs overall survival and progression-free survival compared with cytokines and chemotherapy. Checkpoint inhibitors constitute the up-date of therapeutic approaches, and anti-PD-1 antibody, one checkpoint inhibitor, is now well established as a second and/or third palliative treatment for patients with renal cell carcinoma. In this study, we present the latest data from current studies on cytokines, cancer vaccines, ipilimumab, and nivolumab. The therapeutic efficacies of combinations such as targeted therapy with immune checkpoint inhibitors and anti-CTLA-4 with anti PD-1 (-L1) have been reported in many studies. Preliminary results are encouraging but the high toxicities and elevated cost are limiting. Treatments with combinations of bevacizumab and atezolizumab, axitinib and pembrolizumab or avelumab, lenvatinib and pembrolizumab, and nivolumab and ipilimumab (results from study phase I, II, and sometimes III) are reported to be highly effective and to result in long-lasting responses with response-rates of 70–100%. So far, valid predictors for these therapies have not been forthcoming, but considerable work is being exerted in this area. Heng and Memorial Sloan Kettering Cancer Center (MSKCC) models are still being used to select patients for immunotherapy. Immunotherapy will definitely continue to play an important role in the treatment of patients with renal cell carcinoma; however, many questions remain.

Key words:
renal cell carcinoma – immunotherapy – checkpoint inhibitors – target therapy

Supported by MH CZ – DRO (MMCI, 00209805)

This work was supported by program of the Czech Ministry of Health No. P03-15-34 678A.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
16. 8. 2017

Accepted:
7. 9. 2017


Sources

1. Epidemiologie zhoubných nádorů v České republice. Masarykova univerzita [online]. Dostupné z: http: //www.svod.cz.

2. Ke Q, Costa M. Hypoxia-Inducible Factor-1 (HIF-1). Mol Pharmacol 2006; 70 (5): 1469–1480. doi: 10.1124/mol. 106.027029.

3. Gibney GT, Aziz SA, Camp RL et al. c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma. Ann Oncol 2013; 24 (2): 343–349. doi: 10.1093/annonc/mds463.

4. Gustafsson A, Fritz HKM, Dahlbäck B. Gas6-Axl signaling in presence of Sunitinib is enhanced, diversified and sustained in renal tumor cells, resulting in tumor-progressive advantages. Exp Cell Res 2017; 355 (1): 47–56. doi: 10.1016/j.yexcr.2017.03.040.

5. Graveel CR, Tolbert D, Vande Woude GF. MET: a critical player in tumorigenesis and therapeutic target. Cold Spring Harb Perspect Biol 2013; 5 (7): a009209. doi: 10.1101/cshperspect.a009209.

6. Zhou L, Liu XD, Sun M et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene 2016; 35 (21): 2687–2697.

7. Študentová H, Melichar B. Nový mechanizmus v léčbě karcinomu ledviny: m-TOR – nová cílová struktura. Onkologie 2010; 4 (3): 185–188.

8. Hahn AW, Gill DM, Pal SK et al. The future of immune checkpoint cancer therapy after PD-1 and CTLA-4. Immunotherapy 2017; 9 (8): 681–692. doi: 10.2217/imt-2017-0024.

9. Hammers HJ, Plimack ER, Infante JR et al. Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study. J Clin Oncol 2017; JCO2016721985. doi: 10.1200/JCO.2016.72.1985.

10. Santoni M, Berardi R, Amantini C et al. Role of natural and adaptive immunity in renal cell carcinoma response to VEGFR-TKIs and mTOR inhibitor. Int J Cancer 2014; 134 (12): 2772–2777. doi: 10.1002/ijc.28503.

11. Motzer RJ, Bacik J, Murphy BA et al. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002; 20 (1): 289–296. doi: 10.1200/JCO.2002.20.1.289.

12. Vyzula R, Adámková Krákorová D, Arenberger P (eds). Zhoubný novotvar ledviny (C64). In: Modrá kniha České onkologické společnosti. 23. aktualizace. Brno: Masarykův onkologický ústav 2017: 116–119.

13. McDermott DF, Regan MM, Clark JI et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 2005; 23 (1): 133–141. doi: 10.1200/JCO.2005.03.206.

14. McDermott DF, Cheng SC, Signoretti S et al. The high-dose aldesleukin „select“ trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res 2015; 21 (3): 561–568. doi: 10.1158/1078-0432.CCR-14-1520.

15. Atzpodien J, Hoffmann R, Franzke M et al. Thirteen-year, long-term efficacy of interferon 2alpha and interleukin 2-based home therapy in patients with advanced renal cell carcinoma. Cancer 2002; 95 (5): 1045–1050. doi: 10.1002/cncr.10783.

16. Rini BI, Stenzl A, Zdrojowy R et al. IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol 2016; 17 (11): 1599–1611. doi: 10.1016/S1470-2045 (16) 30408-9.

17. Amin A, Dudek AZ, Logan TF et al. 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 2015; 3: 14. doi: 10.1186/s40425-015-0055-3.

18. Motzer RJ, Escudier B, McDermott DF et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015; 373 (19): 1803–1813. doi: 10.1056/NEJMoa1510665.

19. Escudier BJ, Motzer RJ, 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 2016; 34 (Suppl 15): abstr. 4509.

20. Escudier B, Sharma P, McDermott DF et al. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma. Eur Urol 2017; pii: S0302-2838 (17) 30099-4. doi: 10.1016/j.eururo.2017.02.010.

21. Giorgi D, Scagliarini S, Basso U et al. Safety and efficacy of nivolumab for metastatic renal cell carcinoma (mRCC): Real world data from an Italian expanded access program (EAP). J Clin Oncol 2017; 35 (Suppl 15): abstr. 4577.

22. Yang JC, Hughes M, Kammula U et al. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother 2007; 30 (8): 825–830. doi: 10.1097/CJI.0b013e318156e47e.

23. Rini BI, Stein M, Shannon P et al. Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma. Cancer 2011; 117 (4): 758–767. doi: 10.1002/cncr.25639.

24. Wallin JJ, Bendell JC, Funke R et al. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun 2016; 7: 12624. doi: 10.1038/ncomms12624.

25. McDermott DF, Atkins MB, Motzer RJ et al. A phase II study of atezolizumab (atezo) with or without bevacizumab (bev) versus sunitinib (sun) in untreated metastatic renal cell carcinoma (mRCC) patients (pts). J Clin Oncol 2017; 35 (Suppl 6): abstr. 431.

26. Dudek AZ, Sica RA, Sidani A et al. Phase Ib study of pembrolizumab in combination with bevacizumab for the treatment of metastatic renal cell carcinoma: big ten cancer research consortium BTCRC-GU14-003. J Clin Oncol 2016; 34 (Suppl 2): abstr. 559.

27. Amin A, Plimack ER, Infante JR et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 2014; 32 (Suppl 5): abstr. 5010.

28. Chowdhury S, McDermott DF, Voss MH et al. A phase I/II study to assess the safety and efficacy of pazopanib (PAZ) and pembrolizumab (PEM) in patients (pts) with advanced renal cell carcinoma (aRCC). J Clin Oncol 2017; 35 (Suppl): abstr. 4506.

29. Atkins MB, Plimack ER, Puzanov I et al. Axitinib in combination with pembrolizumab in patients (pts) with advanced renal cell carcinoma (aRCC): Preliminary safety and efficacy results. Ann Oncol 2016; 27 (Suppl 6): 266–295. doi: 10.1093/annonc/mdw373.01.

30. Choueiri TK, Larkin J, Oya M et al. First-line avelumab + axitinib therapy in patients (pts) with advanced renal cell carcinoma (aRCC): Results from a phase Ib trial. Clin Oncol 2017; 35 (Suppl): abstr. 4504.

31. Taylor M, Dutcus CE, Schmidt E et al. A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEM) in patients with selected solid tumors. Ann Oncol 2016; 27 (6): 266–295. doi: 10.1093/annonc/mdw373.04.

32. Choueiri TK, Hodi FS, Thompson JA et al. Pembrolizumab (pembro) plus low-dose ipilimumab (ipi) for patients (pts) with advanced renal cell carcinoma (RCC): Phase 1 KEYNOTE-029 study. J Clin Oncol 2017; 35 (Suppl 6): abstr. 510.

Labels
Paediatric clinical oncology Surgery Clinical oncology
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#