660 Background: OXA is a new DACH platinum (Pt) with preclinical evidence of activity in vivo and in mammary cell lines. Previous clinical study has shown promising activity both for OXA alone (Ann Oncol 2001 Feb 12(2):179–82) and with FU (JCO 2002 15;20:2551–8) in pretreated MBC. Methods: In order to compare tolerance and activity of OXA/FU to reference regimen FUN in pts pretreated with both T and A, we conduct a randomized phase II-III trial. Pts are assigned either to OXA 130 mg/m2 2 hours IV on day (D) 1 plus FU 750 mg/m2 daily by continuous IV infusion D1 to D5 q 3 wks or VIN 25 mg/m2 IV bolus plus the same FU. Eligibility criteria included relapsing progressive MBC, at least one previous chemotherapy (CT) for MBC, no more than 3 prior CT, previous A, previous T therapy given for MBC in an appropriate dose and schedule, at least one measurable target lesion (RECIST criteria), WHO PS 0–2, adequate baseline organs functions. Stratification factors: institution, best response to T: PR or CR vs no response, visceral site: yes vs no, number of previous chemotherapy lines in metastatic disease: 1 vs 2. Efficacy was evaluated by radiological assessment every 6 wks; responses are confirmed at least 4 wks later. Results: Between 7/00 and 7/02 137 Pts have been randomized in 33 centers (68 in OXA arm and 69 in VIN arm). Main pts characteristics, safety (G 3–4 AE by pts) and efficacy (RR, PFS, OS) results are shown in the table below. The study was prematurely discontinued due to accrual difficulty related to competitive drugs introduced (Capecitabine®) in the same clinical setting. Conclusion: OXA-5FU combination achieve similar results in term of RR, PFS and OS and favorable safety profile when compared to VIN-5FU combination which is one of the most active CT regimen in post taxane MBC. No significant financial relationships to disclose.
555 Background: Trial M77001 investigated trastuzumab (Herceptin; H) in combination with docetaxel (D) vs D alone as first-line treatment in HER2+ MBC and demonstrated significant clinical benefits, including prolonged survival, when H was added to taxane therapy. Here we report updated results 24 months after the last pt entered the trial. Methods: M77001 is a multicentre, randomised trial. Eligibility criteria included: HER2+ disease (95% had IHC 3+ and/or FISH+ disease); no prior chemotherapy for MBC; LVEF >50%. D was given as 100mg/m2 q3w x 6 cycles and H as 4mg/kg loading followed by 2mg/kg wkly until disease progression. Pts progressing on D alone could crossover to receive H. The primary endpoint was ORR, confirmed by an independent radiologist. Results: 94 pts were randomised to each arm (2 pts in the HD arm received no treatment and were excluded). The 24-month cut-off data are shown in the table below. Considerably more pts who received the HD regimen showed long-term survival at the 24-month cut-off analysis. 28 of the HD pts were alive for >3 yrs after randomisation, with 2 pts surviving for >4 yrs (14 and 1 pt, respectively, in the D only group; of the 14 pts who survived >3 yrs several had crossed over to H). H added little to the toxicity profile of D. There are no new safety concerns. The incidence of febrile neutropenia (23% vs 17%) and CHF (2% vs 0%) for HD vs D remains unchanged. Conclusion: In patients with HER2-positive MBC the combination of HD is highly effective and associated with significant clinical benefits over D alone. There is evidence of a long-term survival benefit following the addition of H to the D regimen. These sustainable data strongly support the first-line use of H + taxane in pts with HER2-positive MBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis, Bristol-Myers Squibb, Elan Pharma, Eli Lilly, Italfarmaco Hoffmann-La Roche Roche, sanofi-aventis
