Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification

Purpose: This phase II study evaluated weekly trastuzumab and paclitaxel th erapy in women with HER2-normal and HERS-overexpressing metastatic breast c ancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridisation (FISH) assay results. Patients and Methods: Eligible patients had bidimensionally measurable meta static breast cancer. Up to three prior chemotherapy regimens, including pr ior anthracycline and taxane therapy, were allowed. Trastuzumab 4 mg/kg and paclitaxel 90 mg/m(2) were administered on week I,with trastuzumab 2 mg/kg and paclitaxel 90 mg/m2 administered on subsequent weeks. HERS status was evaluated using four different immunohistochemical assays and FISH. Results: Patients received a median of 25 weekly infusions (range, one to 8 5 infusions). Median delivered paclitaxel dose-intensity was 82 mg/m(2)/wk (range, 52 to 90 mg/m2/wk). The intent-to-treat response rate for all 95 pa tients enrolled was 56.8% (95% confidence interval, 47% to 67%). A response rate of 61.4% (4.5% complete response, 56.8% partial response) was observe d in 88 fully assessable patients. In patients with HERS-overexpressing tum ors, overall response rates ranged from 67% to 81% compared with 41% to 46% in patients with HERS-normal expression (ranges reflect the different assa y methods used to assess HERS status). Differences in response rates betwee n patients with HER2-overexpressing tumors and those with normal HERS expre ssion were statistically significant for all assay methods, with CB11 and T AB250 antibodies and FISH having the strongest significance. Therapy was ge nerally well tolerated, although three patients had serious cardiac complic ations. Conclusion: Weekly trastuzumab and paclitaxel therapy is active in women wi th metastatic breast cancer. Therapy was relatively well tolerated; however , attention to cardiac function is necessary.