Vascular endothelial growth factor and programmed death-1 pathway inhibitors in renal cell carcinoma

Charlene M Mantia, David F McDermott, Charlene M Mantia, David F McDermott

Abstract

Advanced renal cell carcinoma has historically carried a poor prognosis with very limited treatment options. However, in recent years, the treatment landscape has changed drastically, with many new therapeutic options and improved survival for patients. Novel treatments consist of molecularly targeted agents against the vascular endothelial growth factor (VEGF) pathway as well as the immune checkpoint inhibitors, which stimulate an antitumor immune response. Recent strategy has focused on the development of combination therapy with the use of VEGF inhibitors and immune checkpoint inhibitors in the first-line setting. As more treatments are approved and the options for therapy expand further, there is a growing need for predictive biomarkers to personalize treatment choices for individual patients. Prospective clinical trials comparing the sequencing of treatments are needed to help determine the best therapeutic approach.

Keywords: combination drug therapy; immunotherapy; programmed cell death 1 receptor; renal cell carcinoma; vascular endothelial growth factors (VEGF).

Conflict of interest statement

COI Disclosures: CMM has nothing to disclose. DFM discloses consulting support from BMS, Pfizer, Merck, Novartis, Exelixis, Array BioPharm, Genentech BioOncology, Alkermes Inc, Jounce Therapeutics, X4 Pharma, Peloton Therapeutics, EMD Serono, Eli Lily and Company and research support from BMS, Prometheus Laboratories, Merck, Genentech, Pfizer, Exelixis, Novartis, X4 Pharma, Alkermes Inc, Peloton.

© 2019 American Cancer Society.

References

    1. SEER. Cancer Stat Facts: Kidney and Renal Pelvis Cancer National Cancer Institute. . Accessed February 22 2019.
    1. Inamura K Renal Cell Tumors: Understanding Their Molecular Pathological Epidemiology and the 2016 WHO Classification. Int J Mol Sci 2017;18(10):2195.
    1. Rini B, Campbell SC, Escudier B. Renal cell carcinoma. The Lancet 2009;373(9669):1119–1132.
    1. Hsieh JJ, Purdue MP, Signoretti S, et al. Renal cell carcinoma. Nat Rev Dis Primers 2017;3:17009.
    1. Rini BI, Atkins MB. Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol 2009;10(10):992–1000.
    1. Cohen RB, Oudard S. Antiangiogenic therapy for advanced renal cell carcinoma: Management of treatment-related toxicities. Invest New Drugs 2012;30:2066–2079.
    1. Sharma SG, Nanda S, Longo S. Anti-Angiogenic Therapy in Renal Cell Carcinoma. Recent Patents on Anti-Cancer Drug Discovery 2010;5(1):77–83.
    1. Escudier B, Eisen T, Stadler W, et al. Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma. N Engl J Med 2007;356(2):125–134.
    1. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma. N Engl J Med 2007;356(2):115–124.
    1. Motzer RJ, Hutson TE, Tomczak P, et al. Overall Survival and Updated Results for Sunitinib Compared with Interferon Alpha in Patients With Metastatic Renal Cell Carcinoma. J Clin Oncol 2009;27(22):3584–3590.
    1. Rini BI, Halabi S, Rosenberg JE, 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): 5422–5428.
    1. Rini BI, Halabi S, Rosenberg JE, et al. Phase III Trial of Bevacizumab Plus Interferon Alfa Versus Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Final Results of CALGB 90206. J Clin Oncol 2010;28(13):2137–2143.
    1. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in Locally Advanced or Metastatic Renal Cell Carinoma: Results of a Randomized Phase III Trial. J Clin Oncol 2010;28(6):1061–1068.
    1. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma. N Engl J Med 2013;369(8):722–31.
    1. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015;373(19):1814–1823.
    1. Choueiri TK, 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 2016;17(7):917–927.
    1. Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. J Clin Oncol 2017;35(6):591–597.
    1. Choueiri TK, Hessel C, Halabi S, et al. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update. European Journal of Cancer 2018;94:115–125.
    1. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011;378(9807):1931–9.
    1. Motzer RJ, Escudier B, Tomczak P, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 2013;14(6):552–62.
    1. Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol 2013;14(3):1287–1294.
    1. Hutson TE, Al-Shukri S, Stus VP, et al. Axitinib Versus Sorafenib in First-Line Metastatic Renal Cell Carcinoma: Overall Survival From a Randomized Phase III Trial. Clin Genitourin Cancer 2017;15(1):72–76.
    1. Motzer RJ, Hutson TE, 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 2015;16:1473–82.
    1. Massari F, Santoni M, Ciccarese C, et al. PD-1 Blockade therapy in renal cell carcinoma: current studies and future promises. Cancer Treat Rev 2015;41(2):114–21.
    1. Janiszewska AD, Poletajew S, Wasiutynski A. Spontaneous regression of renal cell carcinoma. Contemp Oncol (Pozn) 2013; 17(2):123–127.
    1. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. 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.
    1. 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):133–41.
    1. Upton MP, Parker RA, Youmans A, McDermott DF, Atkins MB. Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy. J Immunother 2005;28(5):488–95.
    1. Brahmer J, Drake C, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28:3167–3175.
    1. 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.
    1. Choueiri TK, Fishman MN, Escudier BJ, et al. Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma (mRCC). Clin Cancer Res 2016;22(22):5461–71.
    1. McDermott DF, Lee JL, Szczylik C, et al. Pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (accRCC): Results from cohort A of KEYNOTE-427. J Clin Oncol 2018;36(15_suppl):4500–4500.
    1. Vaishampayan UN, Schoffski P, Ravaud A, et al. First-line (1L) or second-line (2L) avelumab monotherapy in patients (pts) with advanced renal cell carcinoma (aRCC) enrolled in the phase 1b JAVELIN Solid Tumor trial. Annals of Oncology 2018;29 (suppl_8): viii303–viii331.
    1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015;373:23–34.
    1. Wolchuk JD, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Comined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med 2017;377:1345–1356.
    1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 2018;378(14):1277–1290.
    1. Kusmartsev S, Eruslanov E, Kubler H, et al. Oxidative Stress Regulates Expression of VEGFR1 in Myeloid Cells: Link to Tumor-Induced Immune Suppression in Renal Cell Carcinoma. The Journal of Immunology 2008;181:346–353.
    1. Osada T, Chong G, Tansik R, et al. The Effect of Anti-VEGF therapy on Immature Myeloid Cell and Dendritic Cells in Cancer Patients. Cancer Immunol Immunother 2008;57(8):1115–1124.
    1. 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.
    1. Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. The Lancet 2019; DOI: 10.1016/S0140-6736(19)30723-8. [Epub ahead of print]
    1. Rini BI, Plimack ER, Gafanov R, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma [published online ahead of print February 16, 2019]. N Engl J Med 2019. DOI: 10.1056/NEJMoa1816714.
    1. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma [published online ahead of print February 16, 2019]. N Engl J Med 2019. DOI: 10.1056/NEJMoa1816047.
    1. McDermott DF, Huseni MA, Atkins MB, et al. Clinical Activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nature Medicine 2018;24:749–757.
    1. Auvray M, Auclin E, Barthelemy P, et al. Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma. Eur J Cancer 2019;108:33–40.
    1. Dudani S, Graham J, Wells C, et al. First-line immuno-oncology combination therapies in metastatic renal cell carcinoma: Preliminary results from the International Metastatic Renal Cell Carcinoma Database Consortium. J Clin Oncol 37, 2019. (suppl 7S; abstr 584).
    1. Gul A, Shah N, Mantia C, et al. Ipilimumab plus nivolumab as salvage therapy in patients with immunotherapy-refractory metastatic renal cell carcinoma. J Clin Oncol 37, 2019. (suppl 7S; abstr 669).
    1. Patel SP, Kurzrock R. PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol Cancer Ther 2015;14(4):847–56.
    1. Iacovelli R, Nole F, Verri E, et al. Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. Targ Oncol 2016;11(2):143–148.
    1. Rizvi NA, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 2015;348(6230): 124–128.
    1. Carbone DP, Reck M, Paz-Ares L, et al. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med 2017;376:2415–2426.
    1. Voss MH, Fengshen K, Chen D, et al. Integrated biomarker analysis for 412 renal cell cancer (RCC) patients (pts) treated on the phase 3 COMPARZ trial: Correlating common mutation events in PBRM1 and BAP1 with angiogenesis expression signatures and outcomes on tyrosine kinase inhibitor (TKI) therapy. J Clin Oncol 2017;35:4523.
    1. Miao D, Margolis CA, Wenhua Gao, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science 2018;359(6377):801–806.

Source: PubMed

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