Efficacy and safety of trastuzumab plus vinorelbine as second-line treatment for women with HER2-positive metastatic breast cancer beyond disease progression

1094 Background: There is increasing evidence that women with HER2-positive metastatic breast cancer (MBC) benefit from continued trastuzumab (H) therapy beyond disease progression (PD). In a Phase II multicentre 2-step trial we evaluated women for their response to second-line treatment with H + vinorelbine (N) following PD after receiving first-line H + taxane for HER2-positive MBC. Methods: Women aged =18 years with HER2-positive MBC received H (8 mg/kg loading dose followed by 6 mg/kg q3w or 4 mg/kg loading dose followed by 2 mg/kg qw) + N (30 mg/m2 days 1 and 8 q3w) until PD. The primary end point was overall response rate (ORR); secondary end points included time to progression, time to treatment failure, overall survival and safety. Data from a planned interim analysis are presented. Results: Seventeen out of a planned 50 patients (pts) were enrolled between June 2003 and October 2006, with a mean age of 54 years (range 42–70). Nine pts had hormone receptor-positive disease at baseline and 17 pts had HER2-positive disease (16 pts IHC 3+; 1 pt IHC 2+ and CISH+). Pts had previously received H in combination with paclitaxel (9 pts) or docetaxel (8 pts) as first-line therapy for MBC. Pts received a median of 6 treatment cycles with H + N (range 2–14), with 2 pts receiving H q3w and 15 pts receiving H qw. ORR was 29%, with 2 pts showing a complete response, 3 pts experiencing a partial response and 4 pts achieving stable disease lasting 6 months. Eight pts experienced PD. Re-treatment with H + N was well tolerated beyond PD, with grade 3/4 haematological toxicities being the most common serious adverse events, leading to a delay and dose reduction of N. No relevant cardiac toxicities were reported, with only 2 grade 1 cardiac events. All pts withdrew, 14 due to PD. Conclusions: This interim analysis indicates that treatment with Herceptin plus chemotherapy beyond PD is active (ORR 29%) and well tolerated, and provides further evidence that re-treatment with H is a promising therapeutic option. Pt accrual is ongoing and updated results will be presented. No significant financial relationships to disclose.