Trastuzumab-treatment beyond progression – the Vienna experience

Abstract

Background: In human breast carcinoma, Her2 (human EGFR related) positivity is well known to be associated with higher increased relapse rate and impaired survival. Trastuzumab (rhMab4D5) is a humanized monoclonal antibody that targets the extracellular domain of Her2, thereby causing cell degradation. While the antibody is firmly established in the first line treatment of Her2 positive metastatic breast cancer and was recently introduced in the adjuvant setting, it is still not known whether antibody therapy should be continued following the failure of one earlier trastuzumab based treatment line. Patients and methods: Here we report the experience of the Medical University of Vienna concerning trastuzumab treatment beyond progression in a total of 94 patients that were included in two clinical trials. Patients were deemed Her2 positive if they scored 3+ on the HercepTest® or were found to have Her2 gene amplification as defined by FISH. Fifty-four patients were treated in a trial of trastuzumab beyond progression; they received at least two lines of antibody based therapy for metastatic disease. Another forty subjects were treated in a phase II study of capecitabine plus trastuzumab. As inclusion criteria for this trial, at least one previous line of trastuzumab based therapy for metastatic disease was required. Results: In the trial of trastuzumab beyond progression, a time to progression (TTP) of 6 months on first line therapy was observed, which was identical to second and beyond second line. Response rate for first line treatment was 42.6%, as compared to 25.9% for second line. Corresponding numbers for clinical benefit rate (CBR=CR+PR+SD>6 months) were 85.2% for first line, and 68.5% for second line respectively. In the trial of capecitabine plus trastuzumab, TTP, which was defined as primary endpoint, was 8 months. We observed an overall response rate of 20%, and a CBR of 70%. Discussion: Currently, no reliable information concerning the efficacy of trastuzumab beyond progression is available from randomized trials. There is however published evidence from a total of nine studies that point at a possible advantage from continued antibody therapy. Therefore, a direct comparison of this strategy with other treatment options, especially lapatinib based combinations, appears highly warranted.