BATON-CRC: A phase II randomized trial comparing tivozanib plus mFOLFOX6 with bevacizumab plus mFOLFOX6 in stage IV metastatic colorectal cancer

Clinical Cancer Research

Volumn 22, Issue 20, 2016, Pages 5058-5067

  Benson, Al B ^a   Kiss, Igor ^b   Bridgewater, John ^c   Eskens, Ferry A L M ^d   Sasse, Carolyn ^e   Vossen, Sandra ^e   Chen, Jihong ^e   Van Sant, Chip ^e   Ball, Howard A ^e   Keating, Anne ^e   Krivoshik, Andrew ^e  

^a NORTHWESTERN UNIVERSITY   (United States)

^b MASARYK MEMORIAL CANCER INSTITUTE   (Czech Republic)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d ERASMUS MC CANCER INSTITUTE   (Netherlands)

^e ASTELLAS PHARMA GLOBAL DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BEVACIZUMAB; FLUOROURACIL; FOLINIC ACID; NEUROPILIN 1; OXALIPLATIN; TIVOZANIB; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; CARBANILAMIDE DERIVATIVE; PLATINUM COMPLEX; QUINOLINE DERIVATIVE; TUMOR MARKER; VASCULOTROPIN RECEPTOR;

ABDOMINAL PAIN; ADULT; AGED; ARTICLE; ASTHENIA; CONSTIPATION; CONTROLLED STUDY; DECREASED APPETITE; DEEP VEIN THROMBOSIS; DIARRHEA; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DUODENUM TUMOR; DYSGEUSIA; DYSPHONIA; EPISTAXIS; FATIGUE; FEMALE; FEVER; GASTROINTESTINAL HEMORRHAGE; HUMAN; HYPERTENSION; LARGE INTESTINE PERFORATION; LIVER HEMORRHAGE; LUNG EMBOLISM; LUNG HEMORRHAGE; MAJOR CLINICAL STUDY; MALE; METASTATIC COLORECTAL CANCER; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OPEN STUDY; OVERALL SURVIVAL; PARESTHESIA; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; POST HOC ANALYSIS; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL; STOMATITIS; THROMBOCYTOPENIA; VOMITING; ANTAGONISTS AND INHIBITORS; BLOOD; CLINICAL TRIAL; COLORECTAL TUMOR; COMPARATIVE STUDY; DISEASE EXACERBATION; DISEASE FREE SURVIVAL; MIDDLE AGED; PATHOLOGY;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BEVACIZUMAB; BIOMARKERS, TUMOR; COLORECTAL NEOPLASMS; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; FEMALE; FLUOROURACIL; HUMANS; LEUCOVORIN; MALE; MIDDLE AGED; NEUROPILIN-1; ORGANOPLATINUM COMPOUNDS; PHENYLUREA COMPOUNDS; QUINOLINES; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR;

EID: 84991813275     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-3117     Document Type: Article

References (45)

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer Statistics, 2014. CA Cancer J Clin 2014;64:9-29.
2. Sineshaw HM, Robbins AS, Jemal A. Disparities in survival improvement for metastatic colorectal cancer by race/ethnicity and age in the United States. Cancer Causes Control 2014;25:419-23.
3. Bergsland EK. Combination therapies in colorectal cancer treatment. Hematol Oncol Clin N Am 2015;29:85-116.
4. Gustavsson B, Carlsson G, Machover D, Petrelli N, Roth A, Schmoll HJ, et al. A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clin Colorectal Cancer 2015;14:1-10.
5. Akhtar R, Chandel S, Sarotra P, Medhi B. Current status of pharmacological treatment of colorectal cancer. World J Gastrointest Oncol 2014;6:177-83.
6. Nakamura K, Taguchi E, Miura T, Yamamoto A, Takahashi K, Bichat F, et al. KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties. Cancer Res 2006;66:9134-42.
7. Eskens FALM, de Jonge MJA, Bhargava P, Isoe T, Cotreau MM, Esteves B, et al. Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases, in a 4-week-on, 2-week-off schedule in patients with advanced solid tumors. Clin Cancer Res 2011;17:7156-63.
8. Haberkorn BCM, Eskens FALM. Structure, development, preclinical and clinical efficacy of tivozanib (KRN-951, AV-951). Future Oncol 2013; 9:13-20.
9. Cotreau MM, Siebers NM, Miller J, Strahs AL, Slichenmyer W. Effects of ketoconazole or rifampin on the pharmacokinetics of tivozanib hydrochloride, a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Clin Pharmacol Drug Dev 2015;4:137-42.
10. Motzer RJ, Nosov D, Eisen T, Bondarenko I, Lesovoy V, Lipatov O, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol 2013;31:3791-9.
11. Mehta A, Sonpavde G, Escudier B. Tivozanib for the treatment of renal cell carcinoma: results and implications of the TIVO-1 trial. Future Oncol 2014;10:1819-26.
12. Moore K, Infante JR, Cotreau MM, Wilson L, Strahs AL, Vargo DL, et al. A phase I cardiac safety and pharmacokinetic study of tivozanib hydrochloride in patients with advanced solid tumors. Clin Pharm Drug Dev 2014;3:284-9.
13. Berge EM, Bowles DW, Flaig TW, Lam ET, Jimeno A. Tivozanib: practical implications for renal cell carcinoma and other solid tumors. Drugs Today 2013;49:303-15.
14. Pal SK, Bergerot PG, Figlin RA. Tivozanib: current status and future directions in the treatment of solid tumors. Expert Opin Investig Drugs 2012;21:1851-9.
15. Fishman MN, Srinivas S, Hauke RJ, Amato RJ, Esteves B, Cotreau MM, et al. Phase Ib study of tivozanib (AV-951) in combination with temsirolimus in patients with renal cell carcinoma. Eur J Cancer 2013; 49:2841-50.
16. Mayer EL, Scheulen ME, Beckman J, Richly H, Duarte A, Cotreau MM, et al. A phase I dose-escalation study of the VEGFR inhibitor tivozanib hydrochloride with weekly paclitaxel in metastatic breast cancer. Breast Cancer Res Treat 2013;140:331-9.
17. Wolpin BM, Ng K, Zhu AX, Abrams T, Enzinger PC, McCleary NJ, et al. Multicenter phase II study of tivozanib (AV-951) and everolimus (RAD001) for patients with refractory, metastatic colorectal cancer. Oncologist 2013;18:377-8.
18. Oldenhuis CN, Loos WJ, Esteves B, van Doorn L, Cotreau MM, Strahs AL, et al. A phase 1b study of the VEGF receptor tyrosine kinase inhibitor tivozanib and modified FOLFOX-6 in patients with advanced gastrointestinal malignancies. Clin Colorectal Cancer 2015;14:18-24.
19. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26:2013-9.
20. Benson AB, Krivoshik A, Van Sant C, Gyuris J, Feng B. Poster A24: Neuropilin-1 as a potential biomarker of progression-free survival benefit for tivozanib + FOLFOX6 versus bevacizumab + FOLFOX6 in metastatic colorectal cancer: post-hoc biomarker analysis of BATON-CRC Phase 2 trial [abstract]. In: Proceedings of the AACR Annual Meeting; 2015 Mar 6; Orlando, FL.
21. Benson AB, Krivoshik A, Van Sant C, Needle M. Neuropilin-1 may be prognostic and identify a subgroup of patients with metastatic colorectal cancer who benefit from tivozanib + mFOLFOX6 compared to bevacizumab + mFOLFOX6 [abstract]. In: Proceedings of the 17th World Congress on Gastrointestinal Cancer; 2015 Jul 1-4; Barcelona, Spain. Abstract nr O-007.
22. Giantonio BJ, Catalono PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007;25:1539-44.
23. Chen Y, Yang Q, Kuang J, Chen SY, Wei Y, Jiang ZM, et al. Efficacy of adding bevacizumab in the first-line chemotherapy ofmetastatic colorectal cancer: evidence from seven randomized clinical trials. Gastroenterol Res Pract 2014;2014:594930.
24. Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol 2014;32:2240-7.
25. Schmoll HJ, Cunningham D, Sobrero A, Karapetis CS, Rougier P, Koski SL, et al. Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a doubleblind, randomized phase III study (HORIZON III). J Clin Oncol 2012; 30:3588-95.
26. Infante JR, Reid TR, Cohn AL, Edenfield WJ, Cescon TP, Hamm JT, et al. Axitinib and/or bevacizumab with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer: a randomized phase 2 study. Cancer 2013;119:2555-63.
27. Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Mahoney MR, O'Neil B, et al. CALGB/SWOG 80405: phase III trial of irinotecan/5-fu/leucovorin (FOLFIRI) or oxaliplatin/5-fu/leucovorin (FOLFOX6) with bevacizumab (bv) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon. Ann Oncol 2014; 25suppl 2:ii105-17.
28. Buchler T, Pavlik T, Melichar B, Bortlicek Z, Usiakova Z, Dusek L, et al. Bevacizumab with 5-fluorouracil, leucovorin, and oxaliplatin versus bevacizumab with capecitabine and oxaliplatin for metastatic colorectal carcinoma: results of a large registry-based cohort analysis. Cancer 2014;14:323.
29. Yamada Y, Takahari D, Matsumoto H, Baba H, Nakamura M, Yoshida K, et al. Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomized phase 3 trial. Lancet Oncol 2013;14:1278-86.
30. Van Cutsem EV, Bajetta E, Valle J, Köhne CH, Hecht JR, Moore M, et al. Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol 2011;29:2004-10.
31. Hecht JR, Trarbach T, Hainsworth JD, Major P, Jäger E, Wolff RA, et al. Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma. J Clin Oncol 2011;29: 1997-2003.
32. Yin C, Jiang C, Liao F, Rong Y, Cai X, Guo G, et al. Initial LDH level can predict the survival benefit from bevacizumab in the first-line setting in Chinese patients with metastatic colorectal cancer. Onco Targets Ther 2014;7:1415-22.
33. Silvestris N, Scartozzi M, Graziano G, Santini D, Lorusso V, Maiello E, et al. Basal and bevacizumab-based therapy-induced changes of lactate dehydrogenases and fibrinogen levels and clinical outcome of previously untreated metastatic colorectal cancer patients: a multicentric retrospective analysis. Expert Opin Biol Ther 2015;15: 155-62.
34. Cetin B, Kaplan MA, Berk V, Ozturk SC, Benekli M, Isikdogan A, et al. Prognostic factors for overall survival in patients with metastatic colorectal carcinoma treated with vascular endothelial growth factor-targeting agents. Asian Pac J Cancer Prev 2012;13:1059-63.
35. Petrelli F, Coinu A, Cabiddu M, Borgonovo K, Lonati V, Ghilardi M, et al. Prognostic factors for survival with bevacizumab-based therapy in colorectal cancer patients: a systematic review and pooled analysis of 11,585 patients. Med Oncol 2015;32:456.
36. Bar J, Spenser S, Morgan S, Brooks L, Cunningham D, Robertson J, et al. Correlation of lactate dehydrogenase isoenzyme profile with outcome in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab or cediranib: retrospective analysis of the HORIZON I study. Clin Colorectal Cancer 2014;13:46-53.
37. Scartozzi M, Giampieri R, Maccaroni E, Del Prete M, Faloppi L, Bianconi M, et al. Pre-treatment lactate dehydrogenase levels as predictor of efficacy of first-line bevacizumab-based therapy in metastatic colorectal cancer patients. Br J Cancer 2012;106:799-804.
38. Whyte S, Pandor A, Stevenson M, Rees A. Bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer. Health Technol Assess 2010;14suppl 2:47-53.
39. Stintzing S, Stremitzer S, Sebio A, Lenz H-J. Predictive and prognostic markers in the treatment of metastatic colorectal cancer (mCRC): personalized medicine at work. Hematol Oncol Clin N Am 2015; 29:43-60.
40. Lin J, Needle M, Gyuris J, Feng B. Circulating neuropilin-1 as a potential biomarker of progression-free survival benefit for tivozanib in metastatic clear cell renal cell carcinoma (RCC): post-hoc biomarker analysis of tivozanib RCC trials [abstract]. In: Proceedings of the 17th Annual Symposium on Anti-Angiogenesis and Immune Therapies for Cancer; 2015 Feb 19-21; La Jolla, CA. Abstract nr A-17.
41. Rini BI, Michaelson MD, Rosenberg JE, Bukowski RM, Sosman JA, Stadler WM, et al. Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. J Clin Oncol 2008;26:3743-8.
42. Harmon CS, DePrimo SE, Raymond E, Cheng AL, Boucher E, Douillard JY, et al. Mechanism-related circulating proteins as biomarkers for clinical outcome in patients with unresectable hepatocellular carcinoma receiving sunitinib. J Transl Med 2011;9:120.
43. Cagnoni G, Tamagnone L. Semaphorin receptors meet receptor tyrosine kinases on the way of tumor progression. Oncogene 2014;33: 4795-802.
44. Pan Q, Chanthery Y, Liang W-C, Stawicki S, Mak J, Rathore N, et al. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 2007;11:53-67.
45. Small HY, Montezano AC, Rios FJ, Savola C, Touyz RM. Hypertension due to antiangiogenic cancer therapy with vascular endothelial growth factor inhibitors: understanding and managing a new syndrome. Can J Cardiol 2014;30:534-43.