Opinion statement
Various targeted immunotherapies have shown efficacy in metastatic renal cell carcinoma (RCC) recently. Specifically, molecules targeting the PD-1/PD-L1 pathway have shown promising results. These agents appear to provide several advantages over previous standard therapies. First, higher objective responses are attained with these agents, many of which are complete and durable. Second, these drugs are associated with less overall treatment-related toxicity. This allows for the testing of various combination therapies that may provide better clinical outcomes. Finally, these novel therapeutics are unique in that they appear to have benefit in a variety of neoplasms, including those with dismal prognosis such as metastatic non-small cell lung cancer (NSCLC). Further investigations are needed to confirm these findings and explore additional applications. The importance of PD-L1 expression on tumor cells on the efficacy of PD-1 and PD-L1 inhibitors is also under investigation. Patient selection based on this expression may optimize the observed clinical benefit. Thus, we believe that new therapeutics such as Anti-PD1 and Anti-PD-L1 antibodies will make a significant impact on cancer treatment in general as well as in the field of kidney cancer.
Similar content being viewed by others
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance.
Keir ME, Francisco LM, Sharpe AH. PD-1 and its ligands in T-cell immunity. Curr Opin Immunol. 2007;19:309–14.
Iwai Y, Ishida M, Tanaka Y, et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99:12293–7.
Thompson RH, Dong H, Lohse CM. Leibovich, et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res. 2007;13:1757–61.
Thompson RH, Gillett MD, Cheville JC, et al. Costimulatory B7-H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A. 2004;101:17174–9.
Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent Anti-Programmed Death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–75.
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of Anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54. In this study, Topalian et al. describe for the first time a PD-1 blocking agent (an Anti-PD-1 antibody) that generated durable objective responses in patients with advanced RCC, melanoma, and non-small cell lung cancer.
Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of Anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012. In this study by Brahmer et al. Anti-PD-L1 antibody resulted in an objective response rate of 6 %–17% with durability in advanced RCC, melanoma, and non-small cell lung cancer.
Topalian SL. Nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: survival and long-term safety in a phase I trial. Am Soc Clin Oncol. 2013. [Abstract #3002].
Drake CG. Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): long-term patient follow-up. Am Soc Clin Oncol. 2013. [Abstract #4514].
Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (Anti-PD-1) in melanoma. N Engl J Med. 2013;369:134–44. In this study by Hamid et al. a novel Anti-PD-1 antibody was shown to produce durable objective responses in patients with advanced melanoma, and interestingly, the response rate did not differ significantly between patients who had received prior Anti-CTLA-4 antibody treatment and those who had not.
Herbst RS. A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. Am Soc Clin Oncol. 2013. [Abstract #3000].
Cho DC. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with metastatic renal cell carcinoma (mRCC). Am Soc Clin Oncol. 2013. [Abstract #4505].
Grosso J. Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (Anti-PD-1, BMS-936558, ONO-4538). Am Soc Clin Oncol. 2013. [Abstract #3016].
Ribas A, Kefford R, Marshall MA, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol. 2013;31:616–22.
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;30:825–30.
Maker AV, Phan GQ, Attia P, et al. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol. 2005;12:1005–16.
Prieto PA, Yang JC, Sherry RM, et al. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res. 2012;18:2039–47.
Infante JR. Clinical and pharmacodynamic (PD) results of a phase I trial with AMP-224 (B7-DC Fc) that binds to the PD-1 receptor. Am Soc Clin Oncol. 2013. [Abstract #3044].
Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122–33. In this study, Wolchok et al. describe for the first time the effect of Anti-PD-1 and Anti-CTLA-4 antibody combination therapy. In patients with advanced melanoma, the objective response rate was as high as 53%, and treatment-related adverse events were manageable and generally reversible.
Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol. 2001;19:1207–25 [Review].
Lissoni P, Malugani F, Bonfanti A, et al. Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1. J Biol Regul Homeost Agents. 2001;15:140–4.
Ko JS, Zea AH, Rini BI, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15:2148–57.
Rini BI, Stein M, Shannon P, et al. Phase I dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma. Cancer. 2011;117:758–67.
Vey N, Bourhis JH, Boissel N, et al. A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission. Blood. 2012;120:4317–23.
Benson Jr DM, Hofmeister CC, Padmanabhan S, et al. A phase 1 trial of the Anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood. 2012;120:4324–33.
Li Y, Bleakley M, Yee C. IL-21 influences the frequency, phenotype, and affinity of the antigen-specific CD8 T cell response. J Immunol. 2005;175:2261–9.
Conflict of Interest
Anasuya Gunturi declares no conflict of interest. David F. McDermott is a consultant to BMS, Genentech, and Merck.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gunturi, A., McDermott, D.F. Potential of New Therapies like Anti-PD1 in Kidney Cancer. Curr. Treat. Options in Oncol. 15, 137–146 (2014). https://doi.org/10.1007/s11864-013-0268-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11864-013-0268-y