BACH: A randomized phase II trial of doxorubicin-cyclophosphamide (AC) versus pegylated liposomal doxorubicin (PLD)-cyclophosphamide-trastuzumab (CCH) followed by paclitaxel-trastuzumab (TH) as adjuvant therapy for HER2-positive breast cancer (BC)—Cardiac safety analysis.

Abstract

559 Background: For patients (pts) with HER2+ BC, concurrent AC-H results in unacceptable cardiotoxicity rates. Substituting PLD for A in an adjuvant regimen may minimize cardiotoxic risk and permit earlier integration of adjuvant H. Methods: Inthis randomized phase II trial, pts with resected lymph node+ or high-risk, node-negative HER2+ BC were stratified by age and randomized (1:2) to: Arm A: AC (60/600 mg/m2 q21d × 4) followed by T 80 mg/m2 + H 2 mg/kg qwk × 12 or Arm B: PLD 35 mg/m2 + C 600 mg/m2 q21d × 4 + H 2 mg/kg/wk × 12, followed by T 80 mg/m2 + H 2 mg/kg qwk × 12. Subsequent H for a total of 1y was given as per institutional standards. Primary objective was incidence of level 1 (cardiac death or severe heart failure with left ventricular ejection fraction [LVEF] drop > 10% to < 50%) and level 2 (asymptomatic/mild heart failure with LVEF drop > 10% to < 50%) cardiac event rates during the 8 cycles of chemotherapy (CT). This analysis reports cardiotoxicity for the entire patient population completing 8 cycles of CT. Results: 181 pts were randomized between 8/2007 and 4/2009; 59 in Arm A and 118 in Arm B were eligible for cardiac toxicity assessment (modified ITT). Median age was 52.5 y (Arm A; range 30-71) and 50.1 y (Arm B; range 20-83); 98.3% in Arm A and 100% in Arm B had ECOG PS 0-1. No level 1 cardiotoxic events were observed in either arm. Three level 2 cardiotoxic events occurred in Arm A (5.1%; 95% CI: 1.1-14.1) and 1 event in Arm B (0.8%; 95% CI: 0.0-4.6). The mean LVEF reduction from baseline to completion of CT in Arm A was 5.3% (SD 6.38), vs. 2.2% (SD 6.25) in Arm B (p = 0.0015). 16.7% of pts in Arm B vs. 11.9% in Arm A experienced a serious adverse event (AE). Grade 3-4 AEs included (Arm A vs. B) alopecia (8.5 vs. 1.7%), PPE (0 vs. 15%), fatigue (0 vs. 1.7%), rash (0 vs. 4.2%), mucositis (0 vs. 2.5%), nausea (3.4 vs. 0%), and febrile neutropenia (6.8 vs. 4.1%). Conclusions: Concurrent CCH followed by TH as adjuvant therapy for HER2+ BC appears to be safe from a cardiac standpoint and did not increase cardiac event rates compared to AC-TH. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Roche Roche, sanofi-aventis, Schering-Plough Roche, University Hospital Leuven