Trastuzumab (T) plus vinorelbine (VNR) as first combination in Her-2 overexpressing patients with metastatic breast cancer

Abstract

3165 Background: T is effective in patients (pts) with Her-2 overexpressing metastatic breast cancer(mbc), especially in combinations with cytostatics. VNR is active agent in mbc. Preclinical data suggests synergistic cytotoxic activity between T and VNR. It is retrospective analysis of tolerability and efficacy of combination weekly intravenous VNR and T in pts with Her-2 positive mbc. Methods: 15 pts treated between Jan 2003 and Dec 2003 with combination of T and VNR were analyzed. Median age was 45,5 years (35–73), median KPS 100% (70–100). Median of metastatic sites was 2 (1–4),localisations were: soft tissue in 11 pts ( 73%), bones 5 pts (33%), lymph nodes 3 pts (20%), liver 5 pts (33%), lungs 4 pts (27%), c.n.s 1pt (7%), others 2 pts(13%). Her-2 overexpression 3+ was confirmed by immunohistochemy in all pts.12 pts were anthracycline pretreated: 10pts as adjuvant, 2 pts as first line of mbc. T and VNR were administrated weekly (T: 4mg/kg initial dose, 2mg/kg maintenance, iVNR 35mg/m2). All pts were assessed for toxicities, 14 pts for tumor response. 12 pts are still under treatment. Results: The ORR was obtained in 6 pts (40%), CR-1( 7%), PR-5 (33%). Median time of treatment duration in responders is 5,5 months (2–7,5) and 5 pts are still under treatment with median time of follow up 6,5 months (mts). In 8 (53%) pts SD was observed with median time of duration response 4,5 mts (3–7). We noted 2 (13%) cases of progressive disease with mTTP 6,5mts. The main toxicities were: neutropenia G3 in 2pts and G1–2 in 12 pts with VNR dose reductions in consequence ( first from 35mg/m2 to 30mg/m2 in 14 pts-93% and second from 30mg/m2 to 25mg/m2 in 8 pts-53%), anaemia in G 3–1 pt, infections without neutropenia G3–1pt and G2–3pts, fatigue G2–2 pts, neurotoxicity G1–4 pts, hiperbilirubinemy G2–1pt. There was no cardiac toxicity. Because of toxicities 33 cycles (10%) from 317 planed cycles of VNR were omitted. Conclusions: This analysis of small group pts suggest that weekly combination of T and VNR is active in Her-2 overexpressing mbc pts in first or second line treatment after anthracycline. Toxicities are acceptable, the main toxicity is neutropenia required dose reduction. No significant financial relationships to disclose.