Author(s): Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN,
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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.
This article was published in J Clin Oncol
and referenced in Biochemistry & Analytical Biochemistry