A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC)

Cancer Chemotherapy and Pharmacology

Volumn 73, Issue 1, 2014, Pages 181-189

  Molina, Ana M ^a   Hutson, Thomas E ^b   Larkin, James ^c   Gold, Anne M ^d   Wood, Karen ^e   Carter, Dave ^e   Motzer, Robert ^a   Michaelson, M Dror ^f  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b TEXAS ONCOLOGY   (United States)

^c ROYAL MARSDEN HOSPITAL   (United Kingdom)

^d EISAI INC   (United States)

^e EISAI CO LTD   (Japan)

^f MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

Author keywords

Antitumor; Everolimus; Lenvatinib; Metastatic renal cell carcinoma; mTOR; VEGF

Indexed keywords

CREATINE KINASE; EVEROLIMUS; LENVATINIB; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; TRIACYLGLYCEROL LIPASE; VASCULOTROPIN INHIBITOR;

ABDOMINAL PAIN; ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ADULT; ADVANCED CANCER; ANEMIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; BODY WEIGHT DISORDER; CANCER COMBINATION CHEMOTHERAPY; CANCER CONTROL; CANCER GROWTH; CANCER PATIENT; CANCER SURVIVAL; CARDIOMYOPATHY; CELLULITIS; CHOLANGITIS; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DECREASED APPETITE; DETERIORATION; DIARRHEA; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG SAFETY; DRUG WITHDRAWAL; DRY SKIN; DYSPNEA; EDEMA; EPISTAXIS; FATIGUE; FEMALE; GASTRITIS; HEART DISEASE; HEART EJECTION FRACTION; HISTOPATHOLOGY; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTENSION; HYPERTRIGLYCERIDEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; KIDNEY METASTASIS; LEUKOCYTE COUNT; LEUKOCYTE DISORDER; LUNG INFECTION; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAUSEA; OPEN STUDY; PATIENT HISTORY OF CHEMOTHERAPY; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL; RASH; STOMACH HEMORRHAGE; TREATMENT DURATION; TREATMENT RESPONSE; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; VOMITING; WEIGHT REDUCTION;

EID: 84892813872     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-013-2339-y     Document Type: Article

References (34)

1. Rini BI, Atkins MB (2009) Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol 10:992-1000. doi: 10.1016/S1470-2045(09)70240-2
2. Eichelberg C, Junker K, Ljungberg B, Moch H (2009) Diagnostic and prognostic molecular markers for renal cell carcinoma: a critical appraisal of the current state of research and clinical applicability. Eur Urol 55:851-863. doi: 10.1016/j.eururo.2009.01.003
3. Hutson TE (2011) Targeted therapies for the treatment of metastatic renal cell carcinoma: clinical evidence. Oncologist 16(suppl 2):14-22. doi: 10.1634/theoncologist.2011-S2-14
4. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A, RECORD-1 Study Group (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116:4256-4265. doi: 10.1002/cncr.25219
5. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer, Version 1. (2013). http://file3.baitianshi.com/upload/res/201212/ c29/9f/5c8d5.pdf. Accessed 20 Feb 2013
6. Santos N, Wenger JB, Havre P, Liu Y, Dagan R, Imanirad I, Ivey AM, Zlotecki RA, Algood CB, Gilbert SM, Allegra CJ, Okunieff P, Vieweg J, Dang NH, Luesch H, Dang LH (2011) Combination therapy for renal cell cancer: what are possible options? Oncology 81:220-229. doi: 10.1159/000333470
7. Cho IC, Chung J (2012) Current status of targeted therapy for advanced renal cell carcinoma. Korean J Urol 53:217-228. doi: 10.4111/kju.2012.53.4.217
8. Gore ME, Larkin JM (2011) Challenges and opportunities for converting renal cell carcinoma into a chronic disease with targeted therapies. Br J Cancer 104:399-406. doi: 10.1038/sj.bjc.6606084
9. Kaelin WG Jr (2005) The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing. Biochem Biophys Res Commun 338:627-638
10. Staehler M, Rohrmann K, Haseke N, Stief CG, Siebels M (2005) Targeted agents for the treatment of advanced renal cell carcinoma. Curr Drug Targets 6:835-846
11. Brugarolas JB, Vazquez F, Reddy A, Sellers WR, Kaelin WG Jr (2003) TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 4:147-158
12. Thomas GV, Tran C, Mellinghoff IK, Welsbie DS, Chan E, Fueger B, Czernin J, Sawyers CL (2006) Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med 12:122-127
13. Sosman JA, Puzanov I, Atkins MB (2007) Opportunities and obstacles to combination targeted therapy in renal cell cancer. Clin Cancer Res 13(2 Pt 2):764s-769s
14. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M (2008) E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer 122:664-671
15. Boss DS, Glen H, Beijnen JH, Keesen M, Morrison R, Tait B, Copalu W, Mazur A, Wanders J, O'Brien JP, Schellens JH, Evans TR (2012) A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours. Br J Cancer 106:1598-1604. doi: 10.1038/bjc.2012.154
16. Yamada K, Yamamoto N, Yamada Y, Nokihara H, Fujiwara Y, Hirata T, Koizumi F, Nishio K, Koyama N, Tamura T (2011) Phase I dose-escalation study and biomarker analysis of E7080 in patients with advanced solid tumors. Clin Cancer Res 17:2528-2537. doi: 10.1158/1078-0432.CCR-10-2638
17. Sherman SI, Jarzab B, Cabanillas ME, Licitra LF, Pacini F, Martins R, Robinson B, Ball D, McCaffrey J, Shah MH, Bodenner D, Allison R, Newbold K, Elisei R, O'Brien JP, Schlumberger M (2011) A phase II trial of the multitargeted kinase inhibitor E7080 in advanced radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). J Clin Oncol 29(suppl):Abstract 5503
18. Schlumberger M, Jarzab B, Cabanillas ME, Robinson B, Pacini F, Ball DW, McCaffrey JC, Newbold K, Allison R, Martins R, Licitra LF, Shah MH, Bodenner D, Elisei R, Burmeister LA, Funahashi Y, Sellecchia R, Andresen C, O'Brien JP, Sherman SI (2012) A phase II trial of the multitargeted kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer (MTC). J Clin Oncol 30(suppl):Abstract 5591
19. Vergote I, Teneriello M, Powell MA, Miller DS, Garcia AA, Mikheeva ON, Pinter T, Bidzinski M, Cebotaru CL, Fan J, Ren M, Meneses N, Funahashi Y, Kadowaki T, O'Brien JP, Penson RT (2013) A phase II trial of lenvatinib in patients with advanced or recurrent endometrial cancer: angiopoietin-2 as a predictive marker for clinical outcomes. J Clin Oncol 31(suppl):Abstract 5520
20. Fabian MA, Biggs WH 3rd, Treiber DK, Atteridge CE, Azimioara MD, Benedetti MG, Carter TA, Ciceri P, Edeen PT, Floyd M, Ford JM, Galvin M, Gerlach JL, Grotzfeld RM, Herrgard S, Insko DE, Insko MA, Lai AG, Lélias JM, Mehta SA, Milanov ZV, Velasco AM, Wodicka LM, Patel HK, Zarrinkar PP, Lockhart DJ (2005) A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 23:329-336
21. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247. doi: 10.1016/j.ejca.2008.10.026
22. Feldman DR, Baum MS, Ginsberg MS, Hassoun H, Flombaum CD, Velasco S, Fischer P, Ronnen E, Ishill N, Patil S, Motzer RJ (2009) Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 27:1432-1439. doi: 10.1200/JCO.2008.19.0108
23. Sosman JA, Flaherty KT, Atkins MB (2008) Updated results of phase I trial of sorafenib (S) and bevacizumab (B) in patients with metastatic renal cell cancer (mRCC). J Clin Oncol 26(suppl):Abstract 5011
24. Harzstark AL, Small EJ, Weinberg VK, Sun J, Ryan CJ, Lin AM, Fong L, Brocks DR, Rosenberg JE (2011) A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinoma. Cancer 117:4194-4200. doi: 10.1002/cncr.25931
25. Afinitor [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp (2012)
26. Nexavar [prescribing information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc. (2012)
27. Hainsworth JD, Spigel DR, Burris HA 3rd, Waterhouse D, Clark BL, Whorf R (2010) Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma. J Clin Oncol 28:2131-2136. doi: 10.1200/JCO.2009.26.3152
28. Négrier S, Gravis G, Pérol D, Chevreau C, Delva R, Bay JO, Blanc E, Ferlay C, Geoffrois L, Rolland F, Legouffe E, Sevin E, Laguerre B, Escudier B (2011) Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial. Lancet Oncol 12:673-680. doi: 10.1016/S1470-2045(11) 70124-3
29. Harshman LC, Barbeau S, McMillian A, Srinivas S (2013) A phase II study of bevacizumab and everolimus as treatment for refractory metastatic renal cell carcinoma. Clin Genitourin Cancer 11:100-106. doi: 10.1016/j.clgc.2012.12.002
30. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM, TARGET Study Group (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125-134
31. Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD (2006) Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295:2516-2524
32. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, Negrier S, Chevreau C, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Anderson S, Hofilena G, Shan M, Pena C, Lathia C, Bukowski RM (2009) Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 27:3312-3318. doi: 10.1200/JCO.2008.19.5511
33. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061-1068. doi: 10.1200/JCO.2009.23.9764
34. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378:1931-1939. doi: 10.1016/S0140-6736(11)61613-9