New Biweekly Combination of Trastuzumab, Docetaxel and Gemcitabine for HER-2 Positive Metastatic Breast Cancer: Results from a Phase II Multicentric Trial on behalf of Gruppo Oncologico Italia Meridionale

1096 Background: The clinical activity of the combination of chemotherapy plus trastuzumab in HER-2 overexpressing metastatic breast cancer has been well documentated. We report the first results in terms of efficacy and safety of a phase II trial on biweekly combination of trastuzumab plus docetaxel and gemcitabine as first line therapy in HER-2-positive metastatic breast cancer patients. Methods: Patients at first relapse or with synchronous metastasis, were treated with trastuzumab (4 mg/kg, loading dose 6 mg/kg) plus gemcitabine (1000 mg/m2) plus docetaxel (50 mg/m2) as biweekly schedule. Primary end-point was overall response rate (ORR), secondary end-point time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks), and tolerability. Based on previous data, an ORR greater than 60% was considered to indicate clinical activity in this two stage design trial. Results: A total of 26 patients with histologically confirmed, measurable MBC, tumors scored as +3 positive for HER-2 by immuno-histochemistry or FISH +, no pretreated with chemotherapy or trastuzumab for metastatic disease have been enrolled, 22 actually evaluable for response and toxicity. Median age was 49 years (range 34–66), visceral metastases were present in most patients (73%). Median number of cycles was 8 (range 3–12). The ORR was 86% (95% CI, 80–91%), with two CR (9 %) and 17 PR (77%). 3 patients had SD, 1 prolonged (14%). The CBR was 91% (95% CI, 87%-94%). No progression of disease was observed. Median TTP was 7 months (range 5- 9+ months). The worst toxicity was WHO grade 2 neutropenia and grade 2 gastric pain. Conclusions: In this phase II study, the biweekly combination of trastuzumab, gemcitabine, and docetaxel in HER-2-positive breast cancer is very active. The toxicity observed was manageable and did not lead to treatment discontinuation. Thus, the patients accrual is ongoing to the preset target of 50 patients. No significant financial relationships to disclose.