Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer

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

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Abstract

Purpose: To evaluate the efficacy and safety of firstline, 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 [Cl], 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% Cl, 24.4% to 44.7%) and none (95% Cl, 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% Cl, 23.9% to 45.7%) and 7% (95% Cl, 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.

Original languageEnglish
Pages (from-to)719-726
Number of pages8
JournalJournal of Clinical Oncology
Volume20
Issue number3
DOIs
StatePublished - Feb 1 2002
Externally publishedYes

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Breast Neoplasms
Safety
Gene Amplification
Therapeutics
Fluorescence In Situ Hybridization
Immunohistochemistry
erbB-2 Genes
Asthenia
Chills
Trastuzumab
Nausea
Disease Progression
Heart Diseases
Fever
Confidence Intervals
Pain
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. / Vogel, Charles; 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.

In: Journal of Clinical Oncology, Vol. 20, No. 3, 01.02.2002, p. 719-726.

Research output: Contribution to journalArticle

Vogel, C, Cobleigh, MA, Tripathy, D, Gutheil, JC, Harris, LN, Fehrenbacher, L, Slamon, DJ, Murphy, M, Novotny, WF, Burchmore, M, Shak, S, Stewart, SJ & Press, M 2002, 'Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer', Journal of Clinical Oncology, vol. 20, no. 3, pp. 719-726. https://doi.org/10.1200/JCO.20.3.719
Vogel, Charles ; 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. / Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. In: Journal of Clinical Oncology. 2002 ; Vol. 20, No. 3. pp. 719-726.
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abstract = "Purpose: To evaluate the efficacy and safety of firstline, 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 [Cl], 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{\%} Cl, 24.4{\%} to 44.7{\%}) and none (95{\%} Cl, 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{\%} Cl, 23.9{\%} to 45.7{\%}) and 7{\%} (95{\%} Cl, 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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T1 - Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer

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AU - Cobleigh, Melody A.

AU - Tripathy, Debu

AU - Gutheil, John C.

AU - Harris, Lyndsay N.

AU - Fehrenbacher, Louis

AU - Slamon, Dennis J.

AU - Murphy, Maureen

AU - Novotny, William F.

AU - Burchmore, Michael

AU - Shak, Steven

AU - Stewart, Stanford J.

AU - Press, Michael

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N2 - Purpose: To evaluate the efficacy and safety of firstline, 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 [Cl], 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% Cl, 24.4% to 44.7%) and none (95% Cl, 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% Cl, 23.9% to 45.7%) and 7% (95% Cl, 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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