Phase II trial of vinorelbine (V) days 1+8 every 3 weeks and trastuzumab (T) weekly as first-line chemotherapy for HER2+ metastatic breast cancer (MBC)

Abstract

1091 Background: Weekly V and T as 1. line therapy in patients (pts) with HER2+ MBC is highly effective with reported response rates (RR) from 61–86% and median time to progression (TTP) 8.5–16 months. This study examined V given twice every 3 weeks. Methods: Eligible pts had HER2+ (IHC 3+ or FISH) MBC with measurable disease by RECIST criteria, no prior chemotherapy or T for MBC, and LVEF > 50%. They received V 35 mg/m2 i.v. days 1+8 every 3 weeks (= 1 cycle) and T weekly (4 mg/kg loading dose, 2 mg/kg thereafter i.v.) until progression or unacceptable toxicity. Planned sample size was 50, but the study was replaced by a randomised trial at 46 pts, all of them eligible. Primary endpoint was RR, secondary endpoints included TTP, overall survival (OS) and toxicity. Results: From December 2001-July 2004 46 pts were recruited at 4 centers. They received 11 (1–54) cycles (median, range). V dose was reduced due to neutropenia in 7.5% of cycles and for other reasons in 14.5%. V treatment was delayed due to neutropenia in 7.8% of cycles and for other reasons in 4.7% of cycles. Median received V dose intensity was 0,78. Cardiotoxicity: asymptomatic reduction of LVEF > 20% or >10% to below 50%: 8 pts (3 to below 50%). Toxicity grade III-IV (pts): Neutropenia: 11. Infections: 5 (one septic death). Constipation 2. 43 pts have progressed and 32 have died. RR: CR: 9 (20%) PR: 13 (28%) SD 11 (24%) (SD> 6 months 9 (20%)) PD: 10 (22%) NE: 3 (7%). Median duration of response: 18.0 months. Median TTP: 11.0 months (95% confidence interval (95%CI) 7.6–14.4). Median OS: 25.4 months (95%CI 22.7–28.0). After progression 24 received docetaxel, 14 capecitabine, 6 epirubicine, and 11 endocrine therapy. Conclusions: V given twice every 3 weeks and T weekly is a highly active and well-tolerated 1. Line treatment for HER2+MBC. Recruitment into the trial was stopped at 46 pts in favor of a phase III-trial which is ongoing in the Nordic countries comparing V (days 1+8) + T with docetaxel+T every 3 weeks. No significant financial relationships to disclose.