Phase-II study of weekly schedule of trastuzumab, paclitaxel, and carboplatin followed by a week off every 28 days for HER2+ metastatic breast cancer.

BACKGROUND: Addition of carboplatin (C) to trastuzumab (T) and paclitaxel (P) improves the efficacy in HER2+ metastatic breast cancer (MBC). The aim of this phase-II study was to evaluate the efficacy and safety of this combination given weekly (3x) followed by a week off. The primary endpoint was: objective response rate (ORR), and secondary endpoints were: time to progression (TTP), overall survival (OS), and toxicity profile.

METHODS: HER2+ MBC patients were included in the study. Treatment was as follows: T (loading dose:4 mg/kg per week and 2 mg/kg per day thereafter), P (80 mg/m(2)) and C (AUC 2) given weekly 3x, followed by 1 week off until disease progression or unacceptable toxicity.

RESULTS: Forty-one patients (pts) were enrolled-median age: 54.5 years (range 29-75); 87.8% PS 0 or 1; 39 (97.5%) had received prior adjuvant or neoadjuvant treatment; 11 (27%) had received one prior CT line for metastatic disease; disease sites: liver (40%), bone (32.5%), lymph nodes (32.5%) and lung (20%); 19 (47.5%) had > or =2 lesions and 97.5% had measurable disease. A total of 37 pts were evaluated for response: 11(26.8%) CR; 12 (29.3%) PR; 9 (22%) SD; 5 (12.2%) PD and 4 NE, resulting in an ORR of 56.1% (95% CI 39.7-71.5%) and tumor growth control rate (RR + SD) of 78% (95% CI 62.4-89.4%). With a median follow up of 39.4 months, 26 (70.3%) patients have progressed. The median time to progression was 12.3 months (95% CI 8.2-15.5). At the time of this report, ten patients have died. Forty patients received 202 cycles (median five cycles). Grades 3-4 toxicities/pts: 3 (7.5%) anemia, 2 (5%) leucopenia, 10 (25%) neutropenia, 1 (2.5%) febrile neutropenia,1 (2.5%) thrombopenia, 2 (5%) asthenia, 2 (5%) diarrhea, 3 (7.5%) nausea, 2 (5%) vomiting, and 3 (7.5%) mucositis.

CONCLUSIONS: The schedule showed an interesting activity, taking into account that 27% of patients had received previous treatment for MBC. One week of rest may benefit not only the patient but may also improve tolerability and efficacy of the combination.