Impact of trastuzumab treatment beyond disease progression for advanced/metastatic breast cancer on survival - results from a prospective, observational study in Germany.

OBJECTIVES: Evidence suggests that continued trastuzumab therapy beyond progression (TBP) may provide additional survival benefit. Within the framework of an observational prospective study of patients with advanced/metastatic breast cancer receiving trastuzumab in routine clinical practice, we had the opportunity to examine the effect of TBP in a large population. PATIENTS AND METHODS: Among a total of 1843 trastuzumab-treated patients, a sub-cohort of 418 fulfilled the selection criteria for the TBP analysis: 261 continued trastuzumab and 157 discontinued. Logrank tests and Cox models were used to compare survival and identify prognostic factors. RESULTS: Survival from progression was significantly longer in those patients continuing trastuzumab treatment beyond disease progression (TBP: median 22.1 months; no TBP: median 14.9 months; HR = 0.64; P = 0.00021). In addition to TBP, a positive endocrine receptor status, a longer relapse-free interval, no visceral metastasis, no concomitant chemotherapy during first-line treatment, and first-line response were independently significant prognostic variables for longer survival on multivariate analysis. CONCLUSION: The hitherto limited evidence for TBP benefit from randomized studies was confirmed. While a number of strong disease-related predictors for survival after first progression could be identified, the positive effect of trastuzumab continuation retained statistical significance in a multivariate model.

A prospective multicenter phase II study of oral and i.v. vinorelbine plus trastuzumab as first-line therapy in HER2-overexpressing metastatic breast cancer.

BACKGROUND: To evaluate the efficacy and safety of oral and i.v. vinorelbine plus trastuzumab as first-line regimen in a patient-convenient application for human epidermal growth factor receptor 2 (HER2)-overexpressing patients with metastatic breast cancer. PATIENTS AND METHODS: Forty-two women were enrolled in a multicenter study. The patients received i.v. vinorelbine at a dose of 25 mg/m(2) on day 1 followed by oral vinorelbine at a dose of 60 mg/m(2) on days 8 and 15 in a 3-week cycle. Standard dose trastuzumab was given at 3-week intervals. RESULTS: Complete response was observed in 7 patients (18.9%) and partial response in 19 patients (51.4%), for an overall response rate of 70.3% [95% confidence interval (CI) 53.0-84.1]. The disease control rate reached 91.9% (95% CI 78.1-98.3). The median time to progression was 9.3 months, while median overall survival reached 35.6 months. Hematological and non-hematological toxic effects were acceptable with grade 3-4 leukopenia of 14% and neutropenia of 38%; cardiac toxicity did not reach the level of clinical relevance. CONCLUSION: The combination of i.v. and oral vinorelbine plus trastuzumab demonstrates high activity and good tolerability in first-line treatment of HER2-overexpressing metastatic breast cancer. In addition, it offers convenience for the patients with only one i.v. treatment every 3 weeks.