Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer

Purpose: To evaluate the safety and efficacy of weekly docetaxel plus trastuxumab in women with HER-2-overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels. Patients and Methods: Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuxumab as first- or second-line therapy. Both docetaxel 35 mg/m(2)/wk and trastuxumab 2 mg/kg/wk were delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. A loading dose of trastuxumab 4 mg/kg was administered I day before the start of the first cycle. Results: The median delivered dose-intensity of docetaxel was 24 mg/m(2)/wk (range, IS to 27 mg/m(2)/wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval [Cl], 44% to 80%). The ORR in patients whose tumors were HER-2-positive by fluorescence in situ hybridization was 67% (16 of 24 patients, 95% Cl, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% Cl, 53% to 92%), compared with 33% (95% Cl, 7% to 70%) in patients with low HER-2 ECD levels (P = .04). Variations in HER-2 ECD concentrations during treatment correlated with response to treatment. Median time to progression was 9 months. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and excessive tearing became more common with repetitive dosing. Conclusion: Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2-overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy. (C) 2002 by American Society of Clinical Oncology.