Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

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.

M. Cobleigh, C. Vogel, D. Tripathy, N. Robert, S. Scholl, L. Fehrenbacher, J. Wolter, V. Paton, S. Shak, G. Liebérman, D. Slamon
Published 1999 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
PURPOSE Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease. PATIENTS AND METHODS Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals. RESULTS Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events. CONCLUSION Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.
This paper references
10.1073/PNAS.89.22.10578
Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease.
C. T. Guy (1992)
10.1016/0378-1119(94)00866-Q
The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other macromolecular markers--a review.
P. Ravdin (1995)
10.7326/0003-4819-125-1-199607010-00008
Anthracycline-Induced Cardiotoxicity
K. Shan (1996)
10.7326/0003-4819-91-5-710
Risk factors for doxorubicin-induced congestive heart failure.
D. V. Von Hoff (1979)
10.1126/SCIENCE.3798106
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
10.1200/JCO.1998.16.8.2659
Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment.
M. Pegram (1998)
10.1200/JCO.1995.13.10.2567
Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer.
S. Jones (1995)
10.1126/SCIENCE.1659742
Growth factors and cancer.
S. Aaronson (1991)
10.1038/bjc.1993.494
Monoclonal antibodies directed to the erbB-2 receptor inhibit in vivo tumour cell growth.
I. Harwerth (1993)
10.1200/JCO.1995.13.8.2056
Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.
J. Abrams (1995)
10.1126/SCIENCE.2999974
Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
L. Coussens (1985)
10.1200/JCO.1996.14.3.737
Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.
J. Baselga (1996)
10.1073/PNAS.89.10.4285
Humanization of an anti-p185HER2 antibody for human cancer therapy.
P. Carter (1992)
Generation and characterization of monoclonal antibodies specific for the human neu oncogene product, p185.
S. McKenzie (1989)
10.1016/0304-419X(94)90012-4
The biology of erbB-2/neu/HER-2 and its role in cancer.
N. E. Hynes (1994)
10.1093/JNCI/85.5.365
The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.
N. Aaronson (1993)
10.1126/SCIENCE.2885917
erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells.
P. D. Di Fiore (1987)
A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines.
M. C. Hancock (1991)
Current status of salvage chemotherapy for refractory advanced breast cancer
C. Vogel (1996)
10.1126/SCIENCE.3012781
The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity.
T. Akiyama (1986)
10.1073/PNAS.84.20.7159
Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells.
R. Hudziak (1987)
10.1126/SCIENCE.2470152
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
10.1128/MCB.9.3.1165
p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor.
R. Hudziak (1989)
Addition of Herceptin (humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic breast cancer (HER2+/MBC) markedly increases anti-cancer activity: a randomised multinational controlled phase III trial
D. Slamon (1998)
10.1128/MCB.6.5.1729
p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity.
D. F. Stern (1986)



This paper is referenced by
10.2967/jnumed.112.119271
18F-FDG PET/CT for Early Prediction of Response to Neoadjuvant Lapatinib, Trastuzumab, and Their Combination in HER2-Positive Breast Cancer: Results from Neo-ALTTO
G. Gebhart (2013)
10.1517/14712598.2013.767328
Monoclonal antibodies therapies for ovarian cancer
U. Leone Roberti Maggiore (2013)
10.5732/cjc.012.10248
New evidence-based adaptive clinical trial methods for optimally integrating predictive biomarkers into oncology clinical development programs
R. Beckman (2013)
10.1038/nrclinonc.2012.245
Safety and feasibility of targeted agent combinations in solid tumours
S. Park (2013)
10.1007/s13139-010-0068-2
Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression
Z. Liang (2011)
10.1093/annonc/mdq429
Treatment of metastatic breast cancer: second line and beyond.
H. Roché (2011)
10.1038/emm.2013.111
Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade
Rohit Singh (2013)
10.1016/B978-0-12-385467-4.00014-2
Therapeutic Drug Monitoring of Selected Anticancer Drugs: Pharmacogenomics Issues
M. Milone (2012)
10.3816/CBC.2002.N.028
Resistance to trastuzumab: a necessary evil or a temporary challenge?
F. Cardoso (2002)
10.1016/S1548-5315(11)70174-7
Trastuzumab and cardiac toxicity: Monitoring in the adjuvant setting
A. Saad (2007)
10.1016/J.JMB.2007.05.011
Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells.
Yu Zhou (2007)
10.1186/1471-2407-7-153
Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials
G. Viani (2007)
SIGN Guideline No. 84 Management of breast cancer in women
(2005)
10.1016/j.ctrv.2013.09.001
HER2 testing: current status and future directions.
E. Perez (2014)
10.1007/s00432-005-0670-3
The efficacy of trastuzumab in Her-2/neu-overexpressing metastatic breast cancer is independent of p53 status
W. Köstler (2005)
10.1200/JCO.2007.11.2516
Trastuzumab and metastatic breast cancer: trastuzumab use in Australia--monitoring the effect of an expensive medicine access program.
S. Pearson (2007)
10.1002/ijc.21492
Her‐2/neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab‐based therapy in patients with metastatic breast cancer
G. Hudelist (2006)
10.1517/14728210802625671
Emerging drugs in metastatic breast cancer
O. Dizdar (2009)
10.2217/BMT.12.35
Targeted treatments of HER2-positive metastatic breast cancer: trastuzumab and beyond
D. Zardavas (2012)
10.1634/THEONCOLOGIST.11-6-541
Uses and abuses of tumor markers in the diagnosis, monitoring, and treatment of primary and metastatic breast cancer.
N. Henry (2006)
10.1016/j.ejca.2018.07.134
An extended phase Ib study of epertinib, an orally active reversible dual EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours.
H. Arkenau (2018)
10.1007/s10549-018-4755-5
Immunohistochemistry and alternative FISH testing in breast cancer with HER2 equivocal amplification
S. Agersborg (2018)
10.1016/S1874-5784(04)80038-2
4 - HER-2/neu Amplification Detected by Fluorescence in situ Hybridization in Cytological Samples from Breast Cancer
C. Bozzetti (2002)
10.1373/CLINCHEM.2004.046227
Predictive markers in breast and other cancers: a review.
M. Duffy (2005)
10.3919/JJSA.64.2406
EFFICACY OF COMBINATION THERAPY TRASTUZUMAB AND PACLITAXEL OF MULTIPLE BONE METASTASIS FOLLOWING BREAST CANCER SURGERY -A CASE REPORT-
Motoaki Yasukawa (2003)
10.1001/JAMA.291.16.2019
High-quality HER-2 testing: setting a standard for oncologic biomarker assessment.
E. Wiley (2004)
Monoclonal antibodies and side-effect management.
P. M. Muehlbauer (2006)
10.1016/J.CTRV.2006.10.001
The 17q12-q21 amplicon: Her2 and topoisomerase-IIalpha and their importance to the biology of solid tumours.
M. Mano (2007)
10.1158/1541-7786.MCR-06-0367
Integrative Genomic Analysis of Small-Cell Lung Carcinoma Reveals Correlates of Sensitivity to Bcl-2 Antagonists and Uncovers Novel Chromosomal Gains
E. Olejniczak (2007)
10.1158/1078-0432.CCR-07-0163
Phase II Cancer Trials: Out of Control?
B. Chabner (2007)
HER2 POZİTİF METASTATİK MEME KANSERİNDE PTEN, p27 VE PI3K EKSPRESYONUNUN PREDİKTİF VE PROGNOSTİK ÖNEMİ
S. Okutur (2011)
10.1159/000333002
A Case of Metastatic Extramammary Paget's Disease Responding to Trastuzumab plus Paclitaxel Combination Therapy
Fumie Hanawa (2011)
See more
Semantic Scholar Logo Some data provided by SemanticScholar