A phase I-II study of combined blockade of the ErbB receptor network with trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic breast cancer

Clinical Cancer Research

Volumn 14, Issue 19, 2008, Pages 6277-6283

  Arteaga, Carlos L ^a,h   O'Neill, Anne ^b   Moulder, Stacy L ^c   Pins, Michael ^d   Sparano, Joseph A ^e   Sledge, George W ^f   Davidson, Nancy E ^g  

^a VANDERBILT INGRAM CANCER CENTER   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^d NORTHWESTERN UNIVERSITY   (United States)

^e ALBERT EINSTEIN CANCER CENTER   (United States)

^f INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g JOHNS HOPKINS UNIVERSITY   (United States)

^h VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; GEFITINIB; TRASTUZUMAB; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; QUINAZOLINE DERIVATIVE;

ADULT; AGED; ANOREXIA; ARTHRALGIA; ARTICLE; BREAST CANCER; BREAST METASTASIS; CANCER CHEMOTHERAPY; CANCER GROWTH; CLINICAL ARTICLE; CLINICAL TRIAL; CONJUNCTIVAL HYPEREMIA; CONJUNCTIVITIS; CONTROLLED STUDY; CORNEA OPACITY; DIARRHEA; DISEASE SEVERITY; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRY SKIN; DYSPEPSIA; DYSPNEA; ENZYME DEFECT; FATIGUE; FEMALE; FEVER; GENE OVEREXPRESSION; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; HYPERBILIRUBINEMIA; HYPOKALEMIA; LIVER TOXICITY; LUNG TOXICITY; MYALGIA; NAUSEA AND VOMITING; NEPHROTOXICITY; NEUTROPENIA; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHOTOPHOBIA; PNEUMONIA; PRIORITY JOURNAL; PRURITUS; SINGLE DRUG DOSE; SKIN TOXICITY; STOMATITIS; THROMBOCYTOPENIA; TRANSAMINITIS; TREATMENT RESPONSE; BIOSYNTHESIS; BREAST TUMOR; DRUG ANTAGONISM; GENE EXPRESSION REGULATION; METASTASIS; MIDDLE AGED; MORTALITY; PATHOLOGY; PROTEIN BINDING; TREATMENT OUTCOME;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MIDDLE AGED; NEOPLASM METASTASIS; PROTEIN BINDING; QUINAZOLINES; RECEPTOR, ERBB-2; TREATMENT OUTCOME;

EID: 58149153020     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-08-0482     Document Type: Article

References (55)

1. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001;2:127-37.
2. Graus-Porta D, Beerli RR, Daly JM, Hynes NE. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J 1997;16:1647-55.
3. Pinkas-Kramarski R, Soussan L, Waterman H, et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J 1996;15:2452-67.
4. Wang LM, Kuo A, Alimandi M, et al. ErbB2 expression increases the spectrum and potency of ligand-mediated signal transduction through ErbB4. Proc Natl Acad Sci U S A 1998;95:6809-14.
5. Worthylake R, Opresko LK, Wiley HS. ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J Biol Chem 1999;274:8865-74.
6. Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells 1998;16:413-28.
7. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783-92.
8. Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002;20:719-26.
9. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353:1659-72.
10. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673-84.
11. Robert N, Leyland-Jones B, Asmar L, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 2006;24:2786-92.
12. Baselga J, Carbonell X, Castaneda-Soto NJ, et al. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol 2005;23:2162-71.
13. Joensuu H, Kellokump u-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006;354:809-20.
14. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999;17:2639-48.
15. Ritter CA, Perez-Torres M, Rinehart C, et al. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res 2007;13:4909-19.
16. Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 2004;5:317-28.
17. Cho HS, Mason K, Ramyar KX, et al. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003;421:756-60.
18. Motoyama AB, Hynes NE, Lane HA. The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides. Cancer Res 2002;62: 3151-8.
19. Moulder SL, Yakes FM, Muthuswamy SK, Bianco R, Simpson JF, Arteaga CL. Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res 2001;61:8887-95.
20. Diermeier S, Horvath G, Knuechel-Clarke R, Hofstaedter F, Szollosi J, Brockhoff G. Epidermal growth factor receptor coexpression modulates susceptibility to Herceptin in HER2/neu overexpressing breast cancer cells via specific erbB-receptor interaction and activation. Exp Cell Res 2005;304:604-19.
21. Valabrega G, Montemurro F, Sarotto I, et al. TGFα expression impairs Trastuzumab-induced HER2 downregulation. Oncogene 2005;24:3002-10.
22. Moasser MM, Basso A, Averbuch SD, Rosen N. The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res 2001;61:7184-8.
23. Normanno N, Campiglio M, De LA, et al. Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth. Ann Oncol 2002;13:65-72.
24. Anderson NG, Ahmad T, Chan K, Dobson R, Bundred NJ. ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR- positive cancer cell lines with or without erbB2 overexpression. Int J Cancer 2001;94:774-82.
25. Kaplan EL, Meier P. Nonparametric estimation for incomplete observations. J Am Stat Assoc 1958;53:457-81.
26. Tsao M, Sakurada, A, Lorimer I, et al. Molecular analysis of the epidermal growth factor receptor (EGFR) gene and protein expression in patients treated with erlotinib in National Cancer Institute of Canada Clinical Trials Group( NCIC CTG) trial BR-21. Proc Am Soc Clin Oncol 2005;23:622s.
27. Baselga J, Rischin D, Ranson M, et al. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 2002;20: 4292-302.
28. Ranson M, Hammond LA, Ferry D, et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol 2002;20:2240-50.
29. Herbst RS, Maddox AM, Rothenberg ML, et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. J Clin Oncol 2002;20:3815-25.
30. Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 2003;21:2237-46.
31. Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003;290:2149-58.
32. Baselga J, Albanell J, Ruiz A, et al. Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer. J Clin Oncol 2005;23:5323-33.
33. Rothenberg ML, LaFleur B, Levy DE, et al. Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma. J Clin Oncol 2005;23:9265-74.
34. Baselga J, Schoffski P, Rojo F, et al. A phase I pharmacokinetic and pharmacodynamic study of the combination of two anti-EGFR therapies, the monoclonal antibody cetuximab and the tyrosine kinase inhibitor gefitinib, in patients with advanced colorectal, head and neck and non-small-cell lung cancer. Proc Am Soc Clin Oncol 2006;24:122s.
35. Baselga J, Cameron D, Miles D, et al. Objective response rate in a phase II multicenter trial of pertuzumab, a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab in patients with HER2-positive metastatic breast cancer which has progressed during treatment with trastuzumab. Proc Am Soc Clin Oncol 2007;25:33s.
36. Gordon MS, Matei D, Aghajanian C, et al. Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status. J Clin Oncol 2006;24:4324-32.
37. Agus DB, Gordon MS, Taylor C, et al. Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol 2005;23:2534-43.
38. Herbst RS, Davies AM, Natale RB, et al. Efficacy and safety of single-agent pertuzumab, a human epidermal receptor dimerization inhibitor, in patients with non small cell lung cancer. Clin Cancer Res 2007;13:6175-81.
39. Adams CW, Allison DE, Flagella K, et al. Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab. Cancer Immunol Immunother 2006;55:717-27.
40. Agus DB, Akita RW, Fox WD, et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2002;2:127-37.
41. Wong KK, Fracasso PM, Bukowski RM, et al. HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: preliminary phase I results in patients with solid tumors. Proc Am Soc Clin Oncol 2006;24:125s.
42. Albanell J, Rojo F, Averbuch S, et al. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol 2002;20:110-24.
43. Rojo F, Tabernero J, Albanell J, et al. Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma. J Clin Oncol 2006;24:4309-16.
44. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25:1960-6.
45. Wacker B, Nagrani T, Weinberg J, Witt K, Clark G, Cagnoni PJ. Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin Cancer Res 2007;13:3913-21.
46. Chung KY, Shia J, Kemeny NE, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 2005;23:1803-10.
47. Sergina NV, Rausch M, Wang D, et al. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 2007;445:437-41.
48. Arpino G, Gutierrez C, Weiss H, et al. Treatment of human epidermal growth factor receptor 2-overexpressing breast cancer xenografts with multiagent HER-targeted therapy. J Natl Cancer Inst 2007;99:694-705.
49. Rusnak DW, Lackey K, Affleck K, et al. The effects of the novel, reversible epidermal growth factor receptor/ ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther 2001;1:85-94.
50. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006;355:2733-43.
51. Xia W, Husain I, Liu L, et al. Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers. Cancer Res 2007;67:1170-5.
52. Xia W, Bacus S, Hegde P, et al. A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. Proc Natl Acad Sci U S A 2006;103:7795-800.
53. Bayliss J, Hilger A, Vishnu P, Diehl K, El-Ashry D. Reversal of the estrogen receptor negative phenotype in breast cancer and restoration of antiestrogen response. Clin Cancer Res 2007;13:7029-36.
54. Munzone E, Curigliano G, Rocca A, et al. Reverting estrogen-receptor- negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy. Breast Cancer Res 2006;8:R4.
55. Brufsky A, Lembersky B, Schiffman K, Lieberman G, Paton VE. Hormone receptor status does not affect the clinical benefit of trastuzumab therapy for patients with metastatic breast cancer. Clin Breast Cancer 2005;6:247-52.