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Phase II Study of Efficacy, Safety, and Pharmacokinetics of Trastuzumab Monotherapy Administered on a 3-Weekly Schedule

From the Vall d'Hebron, University Hospital, Barcelona; Hospital Arnau de Vilanova, Lleida, Spain; Instituto Nacional De Cancerologia, Tialpan, Mexico; Mutterhaus der Borromaeerinnen, Trier, Germany; Royal Melbourne Hospital, Melbourne, Australia; Auckland Hospital, Auckland, New Zealand; Roche Products Ltd, Welwyn Garden City, United Kingdom

Address reprint requests to José Baselga, Vall d'Hebron, University Hospital, Department of Medical Oncology, Pg Vall d'Hebron, 119-129, E-08035 Barcelona, Spain; e-mail: jbaselga{at}vhebron.net

PURPOSE: This phase II study investigated the efficacy, safety, and pharmacokinetics of trastuzumab monotherapy given as first-line treatment once every 3 weeks (3-weekly) in women with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC).

PATIENTS AND METHODS: Patients with previously untreated HER2-positive MBC received a loading dose of trastuzumab, 8 mg/kg intravenously (IV) and then 6 mg/kg IV at 3-week intervals until disease progression or patient withdrawal.

RESULTS: In total, 105 patients received a median of five cycles of therapy (range, 1 to 35+). The overall response rate was 19% (23% in patients with measurable centrally confirmed immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH] -positive disease) and clinical benefit rate (complete and partial responses plus stable disease for at least 6 months) was 33% (36% in patients with measurable centrally confirmed IHC 3+ and/or FISH-positive disease). Median time to progression was 3.4 months (range, 0.6 to 23.6 months). The most common treatment-related adverse events were rigors, pyrexia, headache, nausea, and fatigue. Median baseline left ventricular ejection fraction was 63%; this did not significantly change over the course of the study. The average exposure to trastuzumab observed in this study was similar to that in previous studies of the weekly regimen. However, as expected, mean trough trastuzumab concentrations were lower and peak levels were higher with 3-weekly trastuzumab compared with weekly treatments.

CONCLUSION: Administering higher doses on a 3-weekly schedule did not compromise the efficacy and safety of trastuzumab in women with HER2-positive MBC, and average exposure was similar to that observed with weekly therapy. Three-weekly trastuzumab may represent a convenient alternative to weekly administration.

Supported by F. Hoffmann-La Roche Ltd.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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