1082 Background: Conventional chemotherapy combined with novel molecular targeted agents has been proven effective and tolerable in metastatic breast cancer (MBC). Taxanes (T) plus bevacizumab (B) and T plus capecitabine (X) showed a benefit in progression free survival (PFS) compared to T alone. Life-threatening or highly symptomatic situations require poly-chemotherapies in MBC patients; therefore a combination of all 3 drugs appears reasonable. Methods: TABEA (NCT01200212) is a prospective, randomized, open label, phase III trial comparing T plus B +/- X as 1st-line therapy in MBC. Patients with histologically confirmed HER2- locally advanced or MBC were included. All patients received T (paclitaxel 80 mg/m2 i.v. d1,8,15 q22 or docetaxel 75 mg/m2 i.v. d1 q22) and B (15 mg/kg i.v. d1 q22) (TB) and were randomized to X (1800 mg/m² daily d1-14 q22) in addition and concurrently to TB (TBX) or TB alone. Randomization was stratified by receptor status, planned taxane, and disease free interval (≤ or >12 months). Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (CR, PR, stable disease ≥ 24 weeks), 3yr overall survival, PFS in patients ≥ 65 years, toxicity, and compliance. Sample size calculation assumed a PFS of 10 and 13.3 months for TB and TBX, respectively (HR=0.75) requiring 432 patients and 386 events with 2-sided α=0.05 and β=0.2. Interim analysis was planned after 25% of required events (n=96). Results: Planned interim futility and safety analyses after 100 documented events in 202 patients have shown no efficacy benefit and higher toxicity in the TBX arm. For PFS, HR=1.061, 95% CI (0.715, 1.576) was observed, futility boundary was crossed. Overall grade 3-4 adverse events (e.g., thrombopenia, diarrhea, hand-foot-syndrome) (72.3 vs. 57.4%, p=0.039)and serious adverse events (40.6 vs. 24.8%, p=0.016) rates were higher for TBX after 16.3 months median follow up. There were 6 deaths in the TBX vs. 1 in the TB arm. Recruitment and therapy were stopped on 5th Oct 2012 following the advice from the IDMC. Conclusions: TABEA failed to show an improvement using the 3 drug regimen TBX in high-risk MBC patients. Clinical trial information: NCT 01200212.
Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane