New agents in renal cell carcinoma

Springer Science and Business Media LLC - Tập 9 - Trang 183-193 - 2013
Raetasha Dabney1, Ryan Devine1, Nancy Sein2, Benjamin George1
1Hematology/Oncology Department, San Antonio Military Medical Center, Fort Sam Houston, USA
2Internal Medicine Department, San Antonio Military Medical Center, Fort Sam Houston, USA

Tóm tắt

Prior to 2005, the treatment options for metastatic renal cell carcinoma (mRCC) were limited. There has been a proliferation of agents since the introduction of sorafenib, sunitinib, and becavicumab for clinical use in advanced renal cell carcinoma. Recently, four new agents have been approved by the US Food and Drug Administration (FDA) for use in mRCC. These agents come from two unique targeted pathways for RCC, tyrosine kinase inhibitors (TKIs) of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors. This review examines the investigational evolution, phases of development, adverse event profiles, and future directions of pazopanib, axitinib, everolimus, and temsirolimus as well as new novel agents being explored in clinical trials for these targeted pathways.

Tài liệu tham khảo

Siegel R, Naishadham D, Jemal A (2005) Cancer statistic 2013. CA Cancer J Clin 63:11–30 Motzer RJ, Mazumdar M, Bacik J et al (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2540 Cohen HT, McGovern FJ (2005) Renal cell carcinoma. NEJM 353(23):2477–2490 National Comprehensive Cancer Network guidelines 1.2013 – Kidney cancer. Available from http://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed February 5, 2013. Coppin C (2010) Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and /or sorafenib. Biogeosciences 25(4):91–101 Albiges L, Salem M, Rini B, Escudier B (2011) Vascular endothelial growth-factor-targeted therapies in advanced renal cell carcinoma. Hematol Oncol Clin North Am 25(4):813–833. doi:10.1016/j.hoc.2011.04.006. Review Kumar A (2012) Targeted therapies in advanced renal cell cancer: a critical review. www.onclive.com. Rini BI, Escudier B, Tomczak P et al (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomized phase 3 trial. Lancet 378:1931–1939 Ward J, Stadler W (2010) Pazopanib in renal cell carcinoma. Clin Cancer Res 16:5923–5927 Hurwitz HI, Dowiati A, Saini S et al (2009) Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res 15:4220–4227 Hutson T, Davis I, Machiels J et al (2010) Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 28:475–480 Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068 Motzer RJ, Hutson TE, Reeves J, et al. (2012) Randomized open-label phase III trial of pazopanib versus sunitinib in first-line treatment of patients with metastatic renal cell carcinoma (MRCC): results of the COMPARZ trial. 2012 ESMO Congress. Abstract LBA8. Presented October 1, 2012. Escudier B, et al. (2012) Patient preference between pazopanib (Paz) and sunitinib: results of a randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma (mRCC)—PISCES study, NCT 01064310. 2012 ASCO Annual Meeting. Abstract CRA4502. Presented June 2, 2012. National Comprehensive Cancer Network. NCCN Guidelines Version 1.2014 Kidney Cancer. N.p., 30 Oct. 2013. Web. 12 Nov. 2013. www.nccn.org. Home. N.p., n.d. Web. 12 Nov. 2013. http://clinicaltrials.gov/ct2/show/NCT01235962?term=PROTECT+trial+pazopanib&rank=1. Rixe O, Bukowski R, Michaelson M et al (2007) Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet 8:975–984 Rugo HS, Herbst RS, Liu G et al (2005) Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol 23:5474–5483 Carmichael C, Lau C, Josephson D et al (2012) Comprehenisve overview of axitinib development in solid malignancies: focus on metastatic renal cell carcinoma. Clin Adv Hematol Oncol 10:307–314 Rini BI, Wilding G, Hudes G et al (2009) Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol 27:4462–4468 Motzer RJ, Escudier B, Tomczak P et al (2013) Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from randomized phase 3 trial. Lancet Oncol 14:552–562 Vezina C, Kudelski A, Seghal SN (1975) Rapamycin (AY-22,989), a new anti-fungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo) 28:721–726 Seghal SN, Baker H, Vezina C (1975) Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation, and characterization. J Antibiot (Tokyo) 28:727–732 Heitman J, Movva NR, Hall MN (1991) Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253:905–909 Faivre S, Kroemer G, Raymond E (2007) Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov 6:599–600 Schuler W, Sedrani R, Cottens S, Haberlin B, Schulz M, Schuurman HJ, Zenke G, Zerwes HG, Schreier MH (1997) SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo. Transplantation 64:36–42 O'Donnell A, Faivre S, Burris HA et al (2008) Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol 26:1588–1595 Tabernero J, Royo F, Burris H, et al. (2005) A phase I study with tumor molecular pharmacodynamic (MPD) evaluation of dose and schedule of the oral mTOR-inhibitor everolimus (RAD001) in patients with advanced solid tumors. J Clin Oncol 23 (suppl): abstr 3007. Amato RJ, Jac J, Geissinger S, Saena S, Willis JP (2009) A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (Everolimus) in patients with metastatic clear cell renal cell cancer. Cancer 115:2438–2446 Motzer RJ, Escudier B, Oudard S et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomized, placebo-controlled phase III trial. Lancet 372:449–456 Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116:4256–4265 Sumanta Kumar P, Robert AF (2011) Future directions of mammalian target of rapamycin (mTOR) inhibitor therapy in renal cell carcinoma. Target Oncol 6(1):5–16 Skotnicki JS, Leone CL, Smith AL (2001) Design, synthesis, and biological evaluation of C-42 hydroxyesters of rapamycin: the identification of CCI-779. Clin Cancer Res 7:3749S–3750S Gibbons JJ, Discafani C, Peterson R (1999) The effect of CCI-779, a novel macrolide anti-tumor agent, on growth of human tumor cells in vitro and in nude mouse xenografts in vivo. Proc Am Assoc Cancer Res 40: 301 (abstr 1000). Geoerger B, Kerr K, Tang CB, Fung KM, Powell B, Sutton LN, Phillips PC, Janss AJ (2001) Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy. Cancer Res 61:1527–1532 Raymond E, Alexandre J, Depenbrock H, Mekhaldi S, Angevin E, Hanauske A, Baudin E, Escudier B, Frisch J, Boni J, Armand JP (2000) CCI-779, a rapamycin analog with antitumor activity: a phase 1 study utilizing a weekly schedule. Proc Am Soc Clin Oncol 19: 187a (abstr 728). Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes G, Park Y, Liou S, Marshall B, Boni JP, Dukart G, Sherman ML (2004) Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 22:909–918 Motzer RJ, Bacik J, Mazumdar M (2004) Prognostic factors for survival of patients with stage IV renal cell carcinoma: Memorial Sloan-Kettering Cancer Center Experience. Clin Cancer Res 10:6302S–6303S Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O’Toole T, Lusgarten S, Moore L, Motzer RJ (2007) Temsirolimus, interferon alfa, or both for advanced renal cell-carcinoma. N Eng J Med 356:2271–2281 Kwitkowski VE, Prowell TM, Ibrahim A, Farrell AT, Justice R, Mitchell S, Sridhara R, Pazfur R (2010) FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma. Oncologist 15:428–435 Pfizer: The World’s Largest Research-based Pharmaceutical Company. Pfizer.com. N.p., May 2012. Web. 12 Nov. 2013. http://labeling.pfizer.com/showlabeling.aspx?id=490. Angevin E, Lopez-Martin JA, Lin CC, Gschwend JE, Harzstark A, Castellano D, Soria JC, Sen P, Chang J, Shi M, Kay A, Escudier B (2013) Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma. Clin Cancer Res. Feb 13. (abstract). http://www.ncbi.nlm.nih.gov/pubmed/23339124. Accessed 30 January 2013. Angevin E et al. (2011) A phase II study of dovitinib (TKI258), an FGFR- and VEGFR-inhibitor, in patients with advanced or metastatic renal cell cancer (mRCC). J Clin Oncol 29 (suppl; abstr 4551). http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview = abst_detail_view&confID = 102&abstractID = 78260. Accessed 30 January 2013 Novartis Pharmaceuticals (2013) An open-label, randomized, multi-center, phase III study to compare the safety and efficacy of dovitinib versus sorafenib in patients with metastatic renal cell carcinoma after failure of anti-angiogenic (VEGF-targeted and mTOR Inhibitor) Therapies. http://www.clinicaltrial.gov/ct2/show/NCT01223027?term = NCT01223027. Accessed 30 January 2013. NLM Identifier: NCT NCT01223027. Nosov DA, Esteves B, Lipatov ON, Lyulko AA, Anischenko AA, Chacko RT, Doval DC, Strahs A, Slichenmyer WJ, Bhargava P (2012) Antitumor activity and safety of tivozanib (AV-951) in a phase II randomized discontinuation trial in patients with renal cell carcinoma. J Clin Oncol 30(14):1678–1685 Motzer, R J. et al. (2012). Tivozanib versus sorafenib as initial targeted therapy for patients with advance renal cell carcinoma: results from a phase III randomize, open-label, multicenter trial. 2012 ASCO meeting abstract 4501. http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview = abst_detail_view&confID = 114&abstractID = 96560. Accessed 30 January 2013. AVEO Pharmaceuticals, Inc (2013) A phase 3, randomized, controlled, multi-center, open-label study to compare tivozanib (AV-951) to sorafenib in subjects with advanced renal cell carcinoma (TIVO-1). http://www.clinicaltrial.gov/ct2/show/NCT01030783. Accessed 30 January 2013. NLM Identifier: NCT01030783. Vaishampayan U (2013) Cabozantinib as a novel therapy for renal cell carcinoma. Curr Oncol Rep 15(2):76–82 Choueiri TK, Pal SK, McDermott DF, et al. (2012) Efficacy of cabozantinib (XL184) in patients (pts) with metastatic, refractory renal cell carcinoma (RCC). 2012 ASCO meeting abstract 4504. http://meetinglibrary.asco.org/content/95382-114. Accessed 24 July 2013. Exelixis (2013). A phase 3, randomized, controlled study of cabozantinib (XL184) vs everolimus in subjects with metastatic renal cell carcinoma that has progressed after prior VEGFR tyrosine kinase inhibitor therapy. http://clinicaltrials.gov/ct2/show/NCT01865747?term = Cabozantinib&rank = 21. Accessed 24 July 2013. NLM Identifier: NCT01865747. van Cruijsen H, Voest EE, Punt CJ, Hoekman K, Witteveen PO, Meijerink MR, Puchalski TA, Robertson J, Saunders O, Jürgensmeier JM, van Herpen CM, Giaccone G (2010) Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours. Eur J Cancer 46(5):901–911 Mulders P, Hawkins R, Nathan P, de Jong I, Osanto S, Porfiri E, Protheroe A, van Herpen CM, Mookerjee B, Pike L, Jürgensmeier JM, Gore ME (2012) Cediranib monotherapy in patients with advanced renal cell carcinoma: results of a randomised phase II study. Eur J Cancer 48(4):527–537 Eisen T, Joensuu H, Nathan PD, Harper PG, Wojtukiewicz MZ, Nicholson S, Bahl A, Tomczak P, Pyrhonen S, Fife K, Bono P, Boxall J, Wagner A, Jeffers M, Lin T, Quinn DI (2012) Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial. Lancet Oncol 13(10):1055–1062 Wong CI, Koh TS, Soo R, Hartono S, Thng CH, McKeegan E, Yong WP, Chen CS, Lee SC, Wong J, Lim R, Sukri N, Lim SE, Ong AB, Steinberg J, Gupta N, Pradhan R, Humerickhouse R, Goh BC (2009) Phase I and biomarker study of ABT-869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies. J Clin Oncol 27(28):4718–4726 Tannir NM, Wong YN, Kollmannsberger CK, Ernstoff MS, Perry DJ, Appleman LJ, Posadas EM, Cho D, Choueiri TK, Coates A, Gupta N, Pradhan R, Qian J, Chen J, Scappaticci FA, Ricker JL, Carlson DM, Michaelson MD (2011) Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure. Eur J Cancer 47(18):2706–2714