Safety and efficacy of combined trastuzumab and CMF therapy in women with metastatic breast cancer: EORTC protocol 10995

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1040 Background: Safety and efficacy of classical CMF combined with 3-weekly Trastuzumab (T), followed by T alone in metastatic breast cancer (MBC). Methods: Patients (pts) with previously treated MBC were enrolled into a Phase II study of T (4 mg/kg then by 2 mg/kg) IV weekly plus CMF, Bonadonna regimen, for a maximum of 8 cycles (cy), followed by T alone (6 mg/kg) IV 3 weekly. Entry criteria included HER2 overexpression, limited anthracycline (A) exposure, normal baseline LVEF and measurable disease (RECIST). Cardiac endpoints were defined as: symptomatic CHF or LVEF drop by ≥ 15% from baseline or to ≥ 5% below lower limit. Results: The trial was closed to recruitment in January 2006, 12 pts are still on treatment. Seventy one pts were entered with a median age of 54 (range 31–75). Forty-one pts had prior CT (32 A), of which 26 adjuvant, 6 MBC, and 9 both adjuvant and MBC. Median PS was 0, 52 pts had visceral disease with a median interval from diagnosis to first relapse of 33.4 months (mo). Out of 70 pts receiving T+CMF (33 pts with 8 cy), 42 continued with T alone for a median duration of 7 cy. Eleven pts discontinued treatment for toxicity (9 on T+CMF, 2 on T alone). To date, the overall response rate is 55% (31/56 pts): 55% (23/42) 1st line; 57% (8/14) 2nd line. An independent review of responses is on-going. Median time to response was 2 mo, median duration of response was 8.3 mo and the median progression free survival was 9.2 mo. The most common grade 3–4 toxicity was neutropenia (53 %). Fourteen pts had cardiac toxicities, one NYHA grade 2 CHF, 6 pts with a drop in LVEF of 15% from baseline after a median of 3 mo of treatment, 9 pts with a drop in LVEF of 5% below LLN, after a median of 8 mo of treatment. The other toxicities included one grade 3 arrhythmia, two grade 3 hypertension, one grade 2 SVT, one grade 3 thrombosis, and one grade 2 dyspnea. One pt previously exposed to A had NYHA grade 4 CHF one year after treatment discontinuation. Conclusions: Combination of T+CMF regimen is feasible treatment for HER2+ MBC patients. The safety profile was acceptable, with cardiac toxicity and neutropenia within previously reported range. Drops in LVEF were mostly asymptomatic irrespective of previous exposure to A. Preliminary response data confirm good efficacy of CMF+T in MBC patients. [Table: see text]