Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer

Vogel, Charles L.; Cobleigh, Melody A.; Tripathy, Debu; Gutheil, John C.; Harris, Lyndsay N.; Fehrenbacher, Louis; Slamon, Dennis J.; Murphy, Maureen; Novotny, William F.; Burchmore, Michael; Shak, Steven; Stewart, Stanford J.; Press, Michael

doi:10.1200/jco.2002.20.3.719

Cited by 1,860HER2/EGFR in Cancer ResearchGastric Cancer Management and OutcomesLung Cancer Treatments and Mutations

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Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer

Vogel, Charles L., Cobleigh, Melody A., Tripathy, Debu, Gutheil, John C., Harris, Lyndsay N., Fehrenbacher, Louis, Slamon, Dennis J., Murphy, Maureen, Novotny, William F., Burchmore, Michael, Shak, Steven, Stewart, Stanford J., Press, Michael·2002·Journal of Clinical Oncology

DOI 10.1200/jco.2002.20.3.719

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Abstract

PURPOSE: To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS: One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. RESULTS: The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. CONCLUSION: Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.

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Previous comparisons of different dosing regimens revealed that trastuzumab or rituximab Cmax did not correlate with clinical efficacy.
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Authors: Vogel, C. L., Cobleigh, M. A., Tripathy, D., Gutheil, J. C., Harris, L. N., Fehrenbacher, L., Slamon, D. J., Murphy, M., Novotny, W. F., Burchmore, M., Shak, S., Stewart, S. J., & Press, M.
Affiliations: University of Southern California (US)
ORCID: Cobleigh, Melody A.
Tripathy, Debu
Harris, Lyndsay N.
Fehrenbacher, Louis
Slamon, Dennis J.
Novotny, William F.
Shak, Steven
Press, Michael
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2002-02-01
Volume: 20
Issue: 3
Pages: 719-726
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2002.20.3.719
OpenAlex: W4239989216
Cited by: 1,860
References: 9
Citations by year: 2026: 12 · 2025: 34 · 2024: 52 · 2023: 75 · 2022: 113 · 2021: 67 · 2020: 72 · 2019: 62 · 2018: 97 · 2017: 95 · 2016: 87 · 2015: 88 · 2014: 71 · 2013: 91 · 2012: 74
FWCI: 32.63
Type: journal article
Language: en
Update notices: new_edition (2023-03-15)
Open access: closed
Locations: Journal of Clinical Oncology (publishedVersion)
Funders: National Cancer Institute (CA48780)
Topics: Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords: trastuzumab, HER2-positive breast cancer, metastatic breast cancer, first-line therapy, single-agent chemotherapy, HER2 immunohistochemistry, HER2 amplification, objective response rate, adverse cardiac events, dose-response relationship, treatment safety

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Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer

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