Abstract #3612: Preliminary results of a phase II trial evaluating efficacy or safety of Trastuzumab plus Vinorelbine as second-line treatment for women with HER2-positive metastatic breast cancer beyond disease progression
Authors: Xavier Durando, Thomas Bachelot, Louis Mauriac, Corinne Delcambre, Philippe Maillart, Corinne Veyret, Jean-Philippe Jacquin, Marie-Ange Mouret-Reynier, Isabelle Van Praagh, Philippe Chollet
Journal: Cancer Research (2009)

Background:  The benefits of subsequent lines of trastuzumab (T) therapy have been increasingly reported for women with HER2-positive metastatic breast cancer (MBC). We report the interim findings of a Phase II multicentre trial evaluating second-line T + vinorelbine (N) in women who received first-line T + taxane therapy for HER2-positive MBC.  Materials and methods:  Women aged \#8805;18 years with HER2-positive (IHC3+/2+ and FISH+) MBC who progressed following first-line T + taxane therapy were enrolled. All patients (pts)    received T (8 mg/kg iv loading dose followed by 6 mg/kg q3w or 4 mg/kg iv loading dose followed by 2 mg/kg qw) + N (30 mg/m 2  days 1 and 8, q3w) until disease progression (PD). The primary end point was overall response rate (ORR); secondary end points included time to progression, overall survival and safety.  Results:  Twenty-one out of 50 patients (pts)    planned were enrolled between June 2003 and April 2008, with a mean age of 56 years [range 42-70]. 11 pts had hormone receptor-positive MBC (7 pts ER+/PgR+; 2 pts ER+/PgR-; 2 pts ER-/PgR+) and 21 pts had HER2[[Unsupported Character - Codename s]]positive disease (16 pts IHC 3+; 4 pts IHC 2+ and CISH+). Prior to enrolling, 14 pts had received previous chemotherapy in the neoadjuvant/adjuvant setting and 7 had undergone adjuvant hormonal therapy. All pts had previously received T in combination with taxanes as first-line therapy for MBC, with 11 pts receiving ongoing T treatment as monotherapy. A median of 5 T + N treatment cycles [range 2-32] were administered. The median follow-up for these 21 patients was 37.3 months [range 7.92-64.07]. ORR was 38%, with 2 pts showing a complete response, 6 pts experiencing a partial response and 4 pts achieving stable disease, and 9 pts experienced PD. Preliminary results showed a median time-to-progression of 3.2 months [range 1.3-17.42]. The median overall survival was 20.1 months [range 1.6-50.7]. The median response duration was 6.6 months [range 1.15-48.5] and the median duration of disease stabilization was 2.5 months [range 2.01-9.04]. The main adverse events were grade 3/4 neutropenia  .   Indeed, for 4 patients this toxicity led to a delay and dose reduction of N. Only two asymptomatic grade 1 cardiac events were reported. No deaths were reported.    Conclusions: This interim analysis indicates that treatment with trastuzumab plus vinorelbine beyond PD is active (ORR 38%) with median duration of response of 6.6 months and well tolerated. Results provide further evidence that treatment beyond progression with trastuzumab is a promising therapeutic option. Pt accrual is ongoing and updated results will be presented.    Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3612.