European Cooperative Trial in Operable Breast Cancer (ECTO): Improved freedom from progression (FFP) from adding paclitaxel (T) to doxorubicin (A) followed by cyclophosphamide methotrexate and fluorouracil (CMF)

513 Background: In the mid 1990’s data indicated that paclitaxel had marked antitumor activity in metastatic breast cancer, justifying the attempt at investigating whether the taxane could improve the therapeutic benefit of established regimens in early breast cancer Methods: From 1996 to 2002 a total of 1355 women with operable breast cancer (T>2cm) were randomized to adjuvant A (75 mg/m2 q21d x 4) followed by i.v. CMF (day 1&8 q28d x 4), or adjuvant A (60 mg/m2) and T (200 mg/m2 over 3 hrs q21d x 4) followed by CMF (AT→CMF), or AT→CMF as primary systemic therapy (PST). Results: Main patient characteristics (T-size, ER/PgR status, grade and age) were evenly distributed among arms. After median follow-up of 43 months, freedom from progression (FFP) was significantly better for women receiving adjuvant AT→CMF than A→CMF (HR 0.65, range 0.48–0.90, P=0.01). In a multivariate analysis, treatment inclusive of paclitaxel stood out as significantly associated with FFP (HR 0.66, P=0.012), together with clinical diameter <4 cm, positive PgR and negative nodal status. FFP was not statistically different between patients receiving AT→CMF as adjuvant or PST (HR 0.83, range 0.59–1.16, P=0.27). Total survival from randomization was not different between arms in the present analysis. As already reported (ASCO 2002, abstract 132) 23% of patients undergoing PST obtained eradication of invasive breast cancer (pCR). Women achieving pCR had a relapse-free survival at 43 months from surgery of 89% v. 74% in women who did not reach pCR (P=0.005). Incidence of local recurrence was low for women undergoing primary surgery (4%) or PST (4.1%). At the almost 5 years of follow up of the present analysis symptomatic cardiac toxicity (Common Toxicity Criteria grade 3) was 0.7% for women receiving A→CMF, and 0.4% for those receiving AT→CMF. Conclusions: The introduction of paclitaxel in the sequence of doxorubicin and CMF improved efficacy without increasing cardiac toxicity. No difference between adjuvant or primary systemic administration of AT→CMF was observed so far. Longer follow-up is needed for conclusive considerations on survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb