P2-18-02: Cardiac Outcomes of Patients on Adjuvant Weekly Paclitaxel (T) and Trastuzumab (H) for Node Negative, HER2 Positive Breast Cancer (BCA).
Authors: Dang C , Tolaney S , Najita J , Gelman R , Yardley D , Marcom K , Albain K , Rugo H , Miller K , Ellis M , Shapira I , Wolff A , Carey L , Vahdat L , Burdette-Radoux S , Budd T , Krop I , Burstein H , Hudis C , Winer E 
Published: June 2012

Abstract
Background
Patients (pts) with (w/) node-negative HER2−positive BCA have a higher risk of recurrence than those with node-negative HER2−negative disease. Several randomized trials have shown the benefit of chemotherapy (most with an anthracycline) and trastuzumab (H) for pts with node-positive and high-risk node-negative BCA. However, the benefit of chemotherapy and H needs to be further explored in the node-negative group. Due to the 2–4% risk of symptomatic congestive heart failure (CHF) with an anthracycline-based treatment (Rx) followed by H, we set out to conduct a study of a taxane-based Rx with H in a node-negative population.
Design: This is a single arm, multicenter, phase II study of paclitaxel (T) (80 mg/m2) and trastuzumab (H) x 12 weekly (w) (4 mg/kg load →2 mg/kg) → H x 52 w (2 mg/kg weekly or 6 mg/kg q 3 w). Pts with HER2−positive BCA (IHC 3 + or FISH amplified at ≥ 2.0) with negative nodes (micrometastasis later allowed) and with a tumor size ≤ 3 cm were enrolled. The primary endpoint is disease-free survival. Secondary endpoints include the incidence of G 3/4 left ventricular systolic dysfunction or congestive heart failure (CHF). Pts had serial left ventricular ejection fraction (LVEF) monitored at baseline (BSLN), and at month (mo) 3, mo 6, and mo 12 w/a multigated acquisition scan or echocardiogram. H was held for significant asymptomatic (Asx) LVEF ↓ (10-15% ↓ from BSLN and &lt; lower limit of normal or ≥ 16% ↓ from BSLN), and H was stopped for CHF.
Results: From 10-9-2007 to 9-3-2010, 406 pts were enrolled. The median (med) age was 55 years (range 23–84 years); 118/406 (29%) had hypertension and 30/406 (7%) had diabetes. As of 6-1-2011, 307 are reported as off Rx of which 261 have completed protocol therapy; 99 remain on therapy. To date, 100%, 94%, 84%, and 83% of pts had LVEF monitoring at BSLN, mo 3, mo 6, and mo 12. The med LVEF at BSLN was 65% (range 50%-81%), at mo 3 was 64% (range 45%-81%), at mo 6 was 64% (range 45%-81%), and at mo 12 was 65% (range 37%-90%). Two pts had CHF; 1 pt had CHF at mo 11 (LVEF was 55% at BSLN and 37% w/CHF event) and 1 pt had CHF at mo 6 (LVEF was 66% at BSLN and 49% w/CHF event). To date, 13 pts had H held for significant Asx LVEF ↓; details on those who had appropriate LVEF recovery and had H restarted will be provided. All patients will have completed 12 mo of Rx by October 2011, and an accurate report of the incidence of CHF will be available.
Conclusion: This represents the cardiac report of pts receiving TH as adjuvant Rx for node-negative (micrometastasis allowed) HER2 positive BCA. Both the CHF events and number of pts w/H hold due to significant Asx ↓ LVEF appear low. Overall, the serial med LVEFs remain stable throughout the 12 mo of Rx. Final data on all 406 pts will be available in December 2011.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-02.