Multicenter study of weekly trastuzumab, paclitaxel, and carboplatin followed by a week of rest every 28 days in patients with HER2+ metastatic breast cancer

Abstract

1080 Background: The addition of carboplatin to trastuzumab and paclitaxel improves the efficacy in HER2+ metastatic breast cancer (MBC). We have conducted a multicenter phase II study to investigate the efficacy and safety of this combination given weekly x 3 followed by 1 week of rest. Primary endpoint was objective response rate and secondary endpoints were time to progression, overall survival and to study the toxicity profile of the combination. Methods: Between August 2003 and April 2006, 40 patients with HER2+ MBC (IHC 3+ or FISH+) have been included in the study. Pats received trastuzumab (loading dose of 4 mg/kg/wk and 2 mg/kg/d following wks), paclitaxel (80 mg/m2) and carboplatin (AUC 2) all given weekly x 3 followed by 1 week of rest. Treatment was given until disease progression or unacceptable toxicity. Results: 40 pats had baseline data available. Median age was 54 yrs (range 29–75). 38 (95%) pats received prior adjuvant or neoadjuvant treatment. 11 (27,5%) pats have received one prior CT line for metastatic disease. 87,5% pats had PS 0 or 1 at study entry. Disease sites were liver 16 (40%), bone 12 (30%), lymph nodes 13 (32.5%) and lung 8 (20%). 19 (47.5%) had 2 lesions. 97.5% had measurable disease. 36 pats have been evaluated for response: 11 CR (31%, 95% CI: 15–46%), 11 PR (31%, 15–36%), 9 SD (25%, 9–36%), 5 PD (14%, 2–26%) and 4 NE resulting in an ORR of 61% (95% CI: 45–77%) and tumor growth control rate (RR+SD) of 86% of patients (95% CI: 75–97%). Median TTP was 12.1 mo (95% CI: 8.8–19.9 mo) and median duration of response and OS have not been reached yet. For a time of observation of 35 mo, the OS is 80,6%. 37 patients have received 194 cycles with a median of 5 cycles. Grade 3–4 toxicities/pats were: 3 (7.5%) anaemia, 2 (5%) leucopenia, 8 (20%) neutropenia, 1 (2.5%) febrile neutropenia, 1 (2.5%) trombopenia, 2 (5%) asthenia, 2 (5%) diarrhea, 3 (7.5%) nausea, 2 (5%) vomiting, 3 (7.5%) mucositis. Conclusions: This interim analysis shows an interesting activity with this regimen. One week of rest may be of better convenience for the patient and hospital but also may improve the tolerability profile and efficacy of the combination. Further results would be available for presentation. No significant financial relationships to disclose.