Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer

International Journal of Cancer

Volumn 135, Issue 8, 2014, Pages 1961-1969

  Hu, Xichun ^a,b   Zhang, Jian ^a,b   Xu, Binghe ^c   Jiang, Zefei ^d   Ragaz, Joseph ^e   Tong, Zhongsheng ^f   Zhang, Qingyuan ^g   Wang, Xiaojia ^h   Feng, Jifeng ⁱ   Pang, Danmei ^j   Fan, Minhao ^a,b   Li, Jin ^a,b   Wang, Biyun ^a,b   Wang, Zhonghua ^a,b   Zhang, Qunling ^a,b   Sun, Si ^a,b   Liao, Chunmei ^a,b  

^a FUDAN UNIVERSITY SHANGHAI CANCER CENTER   (China)

^b FUDAN UNIVERSITY   (China)

^c CANCER HOSPITAL   (China)

^d BEIJING INSTITUTE OF MICROBIOLOGY AND EPIDEMIOLOGY   (China)

^e UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^f TIANJIN MEDICAL UNIVERSITY   (China)

^g HARBIN MEDICAL UNIVERSITY   (China)

^h ZHEJIANG CANCER HOSPITAL   (China)

ⁱ JIANGSU CANCER HOSPITAL   (China)

^j Foshan No 1 People's Hospital   (China)

more..

Author keywords

apatinib; metastatic breast cancer; triple negative; VEGFR2

Indexed keywords

ANTHRACYCLINE; ANTINEOPLASTIC AGENT; APATINIB; TAXANE DERIVATIVE; UNCLASSIFIED DRUG; VASCULOTROPIN INHIBITOR; VASCULOTROPIN RECEPTOR 2;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BILIRUBIN BLOOD LEVEL; BLEEDING; BLOOD SAMPLING; BLOOD TOXICITY; BONE METASTASIS; BRAIN METASTASIS; BREAST METASTASIS; CANCER SURVIVAL; COUGHING; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; FATIGUE; FEMALE; HAND FOOT SYNDROME; HEART ATRIUM FIBRILLATION; HUMAN; HUMAN TISSUE; HYPERTENSION; LEUKOPENIA; LIVER METASTASIS; LUNG HEMORRHAGE; LUNG METASTASIS; LYMPH NODE METASTASIS; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PERICARDIAL EFFUSION; PHASE 2 CLINICAL TRIAL; PLEURA EFFUSION; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN TARGETING; PROTEINURIA; RECOMMENDED DRUG DOSE; SIDE EFFECT; SKIN METASTASIS; STEADY STATE; THROMBOCYTOPENIA; TRIPLE NEGATIVE BREAST CANCER; VISCERAL METASTASIS; VOMITING;

APATINIB; METASTATIC BREAST CANCER; TRIPLE NEGATIVE; VEGFR2;

ADULT; AGED; ANTINEOPLASTIC AGENTS; DISEASE-FREE SURVIVAL; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; LUNG NEOPLASMS; LYMPHATIC METASTASIS; MIDDLE AGED; PYRIDINES; TRIPLE NEGATIVE BREAST NEOPLASMS; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 84905741867     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.28829     Document Type: Article

References (52)

1. Mayer EL, Burstein HJ,. Chemotherapy for metastatic breast cancer. Hematol Oncol Clin North Am 2007; 21: 257-72.
2. Perou CM,. Molecular stratification of triple-negative breast cancers. Oncologist 2011; 16 (Suppl 1): 61-70.
3. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001; 98: 10869-74.
4. Kaplan HG, Malmgren JA, Atwood M,. T1N0 triple negative breast cancer: risk of recurrence and adjuvant chemotherapy. Breast J 2009; 15: 454-60.
5. Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 2003; 100: 8418-23.
6. Kassam F, Enright K, Dent R, et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer 2009; 9: 29-33.
7. Gray R, Bhattacharya S, Bowden C, et al. Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 2009; 27: 4966-72.
8. Miles DW, Chan A, Dirix LY, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 2010; 28: 3239-47.
9. Robert NJ, Dieras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 2011; 29: 1252-60.
10. O'Shaughnessy J, Romieu G, Diéras V, et al. Meta-analysis of patients with triple-negative breast cancer (TNBC) from three randomized trials of first-line bevacizumab (BV) and chemotherapy treatment for metastatic breast cancer (MBC). San Antonio Breast Cancer Symposium 2010 Abstr P6-12-03 2010.
11. Brufsky A, Valero V, Tiangco B, et al. Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial. Breast Cancer Res Treat 2012; 133: 1067-75.
12. Burstein HJ, Elias AD, Rugo HS, et al. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2008; 26: 1810-16.
13. Barrios CH, Liu MC, Lee SC, et al. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer. Breast Cancer Res Treat 2010; 121: 121-31.
14. Bianchi G, Loibl S, Zamagni C, et al. Phase II multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer. Anticancer Drugs 2009; 20: 616-24.
15. Moreno-Aspitia A, Morton RF, Hillman DW, et al. Phase II trial of sorafenib in patients with metastatic breast cancer previously exposed to anthracyclines or taxanes: North Central Cancer Treatment Group and Mayo Clinic Trial N0336. J Clin Oncol 2009; 27: 11-15.
16. Tian S, Quan H, Xie C, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci 2011; 102: 1374-80.
17. Chen P, Iruela-Arispe L, Lou L, et al. VEGFr inhibitor YN968D1 xenograft dose response studies against human colon cancer Ls174t and HT29. Proc Am Assoc Cancer Res 2006; 47:Abstr 1764.
18. Mi YJ, Liang YJ, Huang HB, et al. Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res 2010; 70: 7981-91.
19. Tong XZ, Wang F, Liang S, et al. Apatinib (YN968D1) enhances the efficacy of conventional chemotherapeutical drugs in side population cells and ABCB1-overexpressing leukemia cells. Biochem Pharmacol 2012; 83: 586-97.
20. Mi J, Zhao X, Chen L, et al. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer 2010; 10: 529.
21. Mi J, Qin S, Xu J, et al. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol 2013; 31: 3219-25.
22. Zhang L, Shi MQ, Huang C, et al. A phase II, multicenter, placebo-controlled trial of apatinib in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after two previous treatment regimens. J Clin Oncol 2012; 30s: Abstr 7548.
23. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47.
24. Rugo HS, Roche H, Thomas E, et al. Ixabepilone plus capecitabine vs capecitabine in patients with triple negative tumors: a pooled analysis of patients from two large phase III clinical studies. Cancer Res 2009; 69: 2s:Abstr 3057.
25. Mi D, Chiu H, Gupta V, et al. Validation of a multiplex immunoassay for serum angiogenic factors as biomarkers for aggressive prostate cancer. Clin Chim Acta 2012; 413: 1506-11.
26. Machado DE, Berardo PT, Palmero CY, et al. Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases. J Exp Clin Cancer Res 2010; 29: 4.
27. Wang CJ, Zhou ZG, Holmqvist A, et al. Survivin expression quantified by Image Pro-Plus compared with visual assessment. Appl Immunohistochem Mol Morphol 2009; 17: 530-35.
28. Fox SB, Turley H, Cheale M, et al. Phosphorylated KDR is expressed in the neoplastic and stromal elements of human renal tumours and shuttles from cell membrane to nucleus. J Pathol 2004; 202: 313-20.
29. Fan M, Zhang J, Wang Z, et al. Phosphorylated VEGFR2 and hypertension: potential biomarkers to indicate VEGF-dependency of advanced breast cancer in anti-angiogenic therapy. Breast Cancer Res Treat 2014; 143: 141-51.
30. Wedam SB, Low JA, Yang SX, et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol 2006; 24: 769-77.
31. Yardley DA, Dees EC, Myers SD, et al. Phase II open-label study of sunitinib in patients with advanced breast cancer. Breast Cancer Res Treat 2012; 136: 759-67.
32. Ebos JM, Lee CR, Cruz-Munoz W, et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009; 15: 232-39.
33. Cooke VG, LeBleu VS, Keskin D, et al. Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell 2012; 21: 66-81.
34. Welti JC, Powles T, Foo S, et al. Contrasting effects of sunitinib within in vivo models of metastasis. Angiogenesis 2012; 15: 623-41.
35. Chung AS, Kowanetz M, Wu X, et al. Differential drug class-specific metastatic effects following treatment with a panel of angiogenesis inhibitors. J Pathol 2012; 227: 404-16.
36. Murukesh N, Dive C, Jayson GC,. Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Br J Cancer 2010; 102: 8-18.
37. Deprimo SE, Bello CL, Smeraglia J, et al. Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J Transl Med 2007; 5: 32.
38. Kelly RJ, Rajan A, Force J, et al. Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib. Clin Cancer Res 2011; 17: 1190-99.
39. Zhu AX, Sahani DV, Duda DG, et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 2009; 27: 3027-35.
40. Hanrahan EO, Ryan AJ, Mann H, et al. Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. Clin Cancer Res 2009; 15: 3600-09.
41. Jonasch E, Corn P, Pagliaro LC, et al. Upfront, randomized, phase 2 trial of sorafenib versus sorafenib and low-dose interferon alfa in patients with advanced renal cell carcinoma: clinical and biomarker analysis. Cancer 2010; 116: 57-65.
42. Weigand M, Hantel P, Kreienberg R, et al. Autocrine vascular endothelial growth factor signalling in breast cancer. Evidence from cell lines and primary breast cancer cultures in vitro. Angiogenesis 2005; 8: 197-204.
43. Kranz A, Mattfeldt T, Waltenberger J,. Molecular mediators of tumor angiogenesis: enhanced expression and activation of vascular endothelial growth factor receptor KDR in primary breast cancer. Int J Cancer 1999; 84: 293-98.
44. Barrios CH, Liu MC, Lee SC, et al. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer. Breast Cancer Res Treat 2010; 121: 121-31.
45. Bergh J, Bondarenko IM, Lichinitser MR, et al. First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol 2012; 30: 921-29.
46. Crown J, Dieras V, Staroslawska E, et al. Phase III evaluation of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC). J Clin Oncol 2010; 28: 18s-1011s.
47. Robert NJ, Saleh MN, Paul D, et al. Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial. Clin Breast Cancer 2011; 11: 82-92.
48. Kozloff M, Chuang E, Starr A, et al. An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer. Ann Oncol 2010; 21: 1436-41.
49. Baselga J, Segalla JG, Roche H, et al. Sorafenib in combination with capecitabine: an oral regimen for patients with HER2-negative locally advanced or metastatic breast cancer. J Clin Oncol 2012; 30: 1484-91.
50. Schwartzberg LS, Tauer KW, Hermann RC, et al. Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab. Clin Cancer Res 2013; 19: 2745-54.
51. Gradishar WJ, Kaklamani V, Sahoo TP, et al. A double-blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer. Eur J Cancer 2013; 49: 312-22.
52. Rugo HS, Stopeck AT, Joy AA, et al. Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel vs. docetaxel plus placebo in patients with metastatic breast cancer. J Clin Oncol 2011; 29: 2459-65.