Gemcitabine, paclitaxel plus trastuzumab (GTH) in HER2 ECD-positive metastatic breast cancer

Abstract

740 Background: We have shown that the response of advanced breast cancer to gemcitabine plus paclitaxel in HER2 ECD-positive patients is 42%, while it is 83% in HER2 ECD-negative cases (Ann Onc, 2004). We have now performed a proof-of-concept phase II trial to evaluate whether adding trastuzumab to gemcitabine-paclitaxel is able to reverse the poor response of HER2 ECD-positive metastatic breast cancer, and present here the preliminary results. The objective of the trial was to achieve at least a 66% response rate. Methods: Serum levels of HER2 ECD were screened in 214 cases with histologically confirmed metastatic breast carcinoma, 52 (24%) were positive (>30 ng/ml, Oncogene Science Diagnostics), and 30 patients were enrolled. The GTH regimen was paclitaxel 150 mg/m2 followed by gemcitabine 2500 mg/m2, both on Day 1 of a 14-day cycle, maximum of 10 cycles, and trastuzumab 2 mg/kg weekly, with a loading dose of 4 mg/kg, administered the day before the first chemotherapy dose. Results: Of the 30 cases, 18 are evaluable for toxicity, and 13 for efficacy. Characteristics of non-evaluable cases were: one hypersensitivity reaction to the first trastuzumab dose and two early disease progressions at day 3 and day 8. Median age at diagnosis was 51 years; median performance status was 90; median number of metastatic sites was 2. Most patients (74%) had prior adjuvant chemotherapy, usually involving anthracyclines (68%). Grade 3/4 hematologic toxicities were neutropenia (27%), leukopenia (19%), and thrombocytopenia (1%). No patient had neutropenia and fever. Grade 3/4 nonhematologic toxicities were fatigue (1%), elevation of ALT (6%) or AST (1%), neurosensory (1%), and constipation. Objective response rate was 84% (15% CR; 69% PR); 8% had SD; 8% had PD. Conclusions: The preliminary evaluation of GTH in HER2 ECD-positive metastatic breast carcinoma shows remarkable activity and a favorable toxicity profile. HER2 ECD is a valuable method to select for trastuzumab therapy. Updated results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb; Eli Lilly Eli Lilly