Metastatic renal cell carcinoma regains sensitivity to tyrosine kinase inhibitor after nivolumab treatment: A case report

Azuma,Takeshi; Sugihara,Tohru; Honda,Sachi; Yoshizaki,Uran; Niimi,Fusako; Tsuru,Ibuki; Kume,Haruki

doi:10.3892/ol.2019.10027

Metastatic renal cell carcinoma regains sensitivity to tyrosine kinase inhibitor after nivolumab treatment: A case report

Authors:
- Takeshi Azuma
- Tohru Sugihara
- Sachi Honda
- Uran Yoshizaki
- Fusako Niimi
- Ibuki Tsuru
- Haruki Kume
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Affiliations: Department of Urology, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo 183‑0042, Japan, Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo 113‑8654, Japan
Published online on: February 8, 2019 https://doi.org/10.3892/ol.2019.10027
Pages: 4011-4015

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Abstract

Sequential therapy using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors is the mainstay of treatment for metastatic renal cell carcinoma. Recently, anti‑programmed death‑1 (PD‑1) antibody, a type of immune checkpoint inhibitor, was approved for use against metastatic renal cell carcinoma. In the present report, two cases of TKI‑refractory metastatic renal cell carcinoma which regained sensitivity to TKI after immunotherapy with nivolumab were described. In one case, a third challenge with axitinib after nivolumab treatment resulted in tumor shrinkage, although the second challenge with axitinib immediately before nivolumab treatment had no effect. In another case, a second challenge with pazopanib after nivolumab slightly reduced lung metastasis, which was refractory to pazopanib before nivolumab treatment. These cases suggest that nivolumab can influence the response to subsequent TKI treatment.

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1	Lambea J, Anido U, Etxániz O, Flores L, Montesa Á, Sepúlveda JM and Esteban E: The wide experience of the sequential therapy for patients with metastatic renal cell carcinoma. Curr Oncol Rep. 18:662016. View Article : Google Scholar : PubMed/NCBI
2	Rathmell WK and Chen S: VHL inactivation in renal cell carcinoma: Implications for diagnosis, prognosis and treatment. Expert Rev Anticancer Ther. 8:63–73. 2008. View Article : Google Scholar : PubMed/NCBI
3	Gnarra JR, Tory K, Weng Y, Schmidt L, Wei MH, Li H, Latif F, Liu S, Chen F, Duh FM, et al: Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet. 7:85–90. 1994. View Article : Google Scholar : PubMed/NCBI
4	Cancer Genome Atlas Research Network: Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 499:43–49. 2013. View Article : Google Scholar : PubMed/NCBI
5	Folkman J: The role of angiogenesis in tumor growth. Semin Cancer Biol. 3:65–71. 1992.PubMed/NCBI
6	Ferrara N and Davis-Smyth T: The biology of vascular endothelial growth factor. Endocr Rev. 18:4–25. 1997. View Article : Google Scholar : PubMed/NCBI
7	Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI
8	Tomisawa M, Tokunaga T, Oshika Y, Tsuchida T, Fukushima Y, Sato H, Kijima H, Yamazaki H, Ueyama Y, Tamaoki N and Nakamura M: Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularisation in renal cell carcinoma. Eur J Cancer. 35:133–137. 1999. View Article : Google Scholar : PubMed/NCBI
9	Bhargava P and Robinson MO: Development of second-generation VEGFR tyrosine kinase inhibitors: Current status. Curr Oncol Rep. 13:103–111. 2011. View Article : Google Scholar : PubMed/NCBI
10	Hu-Lowe DD, Zou HY, Grazzini ML, Hallin ME, Wickman GR, Amundson K, Chen JH, Rewolinski DA, Yamazaki S, Wu EY, et al: Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 14:7272–7283. 2008. View Article : Google Scholar : PubMed/NCBI
11	Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, et al: Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 369:722–731. 2013. View Article : Google Scholar : PubMed/NCBI
12	Yuan H, Cai P, Li Q, Wang W, Sun Y, Xu Q and Gu Y: Axitinib augments antitumor activity in renal cell carcinoma via STAT3-dependent reversal of myeloid-derived suppressor cell accumulation. Biomed Pharmacother. 68:751–756. 2014. View Article : Google Scholar : PubMed/NCBI
13	Pal SK, Hossain DM, Zhang Q, Frankel PH, Jones JO, Carmichael C, Ruel C, Lau C and Kortylewski M: Pazopanib as third line therapy for metastatic renal cell carcinoma: Clinical efficacy and temporal analysis of cytokine profile. J Urol. 193:1114–1121. 2015. View Article : Google Scholar : PubMed/NCBI
14	Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 366:2443–2454. 2012. View Article : Google Scholar : PubMed/NCBI
15	Ishida Y, Agata Y, Shibahara K and Honjo T: Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 11:3887–3895. 1992. View Article : Google Scholar : PubMed/NCBI
16	Dong H, Zhu G, Tamada K and Chen L: B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 5:1365–1369. 1999. View Article : Google Scholar : PubMed/NCBI
17	Azuma T, Yao S, Zhu G, Flies AS, Flies SJ and Chen L: B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells. Blood. 111:3635–3643. 2008. View Article : Google Scholar : PubMed/NCBI
18	Schvartsman G, Peng SA, Bis G, Lee JJ, Benveniste MFK, Zhang J, Roarty EB, Lacerda L, Swisher S, Heymach JV, et al: Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer. Lung Cancer. 112:90–95. 2017. View Article : Google Scholar : PubMed/NCBI
19	Ogawara D, Soda H, Iwasaki K, Suyama T, Taniguchi H, Fukuda Y and Mukae H: Remarkable response of nivolumab-refractory lung cancer to salvage chemotherapy. Thorac Cancer. 9:175–180. 2018. View Article : Google Scholar : PubMed/NCBI
20	Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, et al: Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 373:1803–1813. 2015. View Article : Google Scholar : PubMed/NCBI
21	Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al: Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 373:1627–1639. 2015. View Article : Google Scholar : PubMed/NCBI
22	Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al: Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 375:1856–1867. 2016. View Article : Google Scholar : PubMed/NCBI
23	Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, Vaishampayan U, George S, Olencki TE, Tarazi JC, et al: Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: A non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 19:405–415. 2018. View Article : Google Scholar : PubMed/NCBI
24	Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, et al: Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 378:2078–2092. 2018. View Article : Google Scholar : PubMed/NCBI
25	Albiges L, Fay AP, Xie W, Krajewski K, McDermott DF, Heng DY, Dariane C, DeVelasco G, Lester R, Escudier B and Choueiri TK: Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma. Eur J Cancer. 51:2580–2586. 2015. View Article : Google Scholar : PubMed/NCBI
26	Fidler IJ: The pathogenesis of cancer metastasis: The ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 3:453–458. 2003. View Article : Google Scholar : PubMed/NCBI
27	Chen L, Azuma T, Yu W, Zheng X, Luo L and Chen L: B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction. Proc Natl Acad Sci USA. 115:3126–3131. 2018. View Article : Google Scholar : PubMed/NCBI
28	Chiou VL and Burotto M: Pseudoprogression and immune-related response in solid tumors. J Clin Oncol. 33:3541–3543. 2015. View Article : Google Scholar : PubMed/NCBI
29	Fujimoto D, Yoshioka H, Kataoka Y, Morimoto T, Hata T, Kim YH, Tomii K, Ishida T, Hirabayashi M, Hara S, et al: Pseudoprogression in previously treated patients with non-small cell lung cancer who received nivolumab monotherapy. J Thorac Oncol. Nov 20–2018.(Epub ahead of print). View Article : Google Scholar
30	Tsushima F, Yao S, Shin T, Flies A, Flies S, Xu H, Tamada K, Pardoll DM and Chen L: Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy. Blood. 110:180–185. 2007. View Article : Google Scholar : PubMed/NCBI
31	Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman PA, Wood L, Garcia J, et al: Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 15:2148–2157. 2009. View Article : Google Scholar : PubMed/NCBI