Pooled cardiac safety analysis of patients with HER2-positive metastatic breast cancer receiving trastuzumab.

Abstract #6136 Background: The outlook for women with human epidermal growth factor receptor 2 (HER2)-positive early and advanced breast cancer has been significantly improved by the incorporation of trastuzumab (Herceptin ® ; H) into therapeutic regimens. H has a proven safety profile observed over 10 years of clinical experience in >500,000 patients (pts); however some concerns remain over cardiac dysfunction. This retrospective study reports detailed new analyses of pooled cardiac safety data from 6 metastatic breast cancer (MBC) trials.
 Methods: Reports of selected adverse events of symptomatic congestive heart failure (CHF) and cardiac rhythm disturbances (CRDs) as well as left ventricular ejection fraction (LVEF) declines were analysed. As definitions of CHF differed between trials, a detailed manual review of original data was performed, including serious adverse event reports. CRDs were identified based on Medical Dictionary for Regulatory Activities terms. LVEF declines were defined as decreases of ≥15 percentage points (pp) from baseline (BL) or ≥10 pp from BL to an LVEF of ≤50%.
 Results: In total, 882 MBC pts from 6 trials were evaluable for the pooled analysis: in 2 of the trials H was given as monotherapy (WO16229, MO16982) and in others H was combined with paclitaxel (BO15935), docetaxel (M77001), docetaxel and capecitabine (MO16419), and anastrozole (BO16216). There were 683 pts in the H group and 199 in the control group. Pt characteristics were well balanced between treatment groups. Symptomatic CHF was identified in 11 pts (1.6%) in the H group (including 1 death) and none in the control group. Of the 11 pts with CHF, 9 had received prior anthracyclines. Fifty-five CRDs (6.6%) were reported in 45 pts in the H group, with tachycardia (3.2%), palpitations (2.6%) and arrhythmias (0.6%) being the most frequent. With the exception of a single grade 3 event in each group, all CRDs were grade 1 or 2. Nearly all CRDs resolved with no sequelae (50/55 events; 91%). In the control group 2 pts (0.1%) experienced a CRD. The total number of pts evaluable for LVEF decline was 673 in the H group and 194 in the control group; 74 (11.0%) and 7 pts (3.6%), respectively, experienced a drop of ≥10 pp from BL to ≤50%. Eighty-nine (13.2%) and 9 pts (4.6%), respectively, had an LVEF decline of ≥15 pp from BL.
 Discussion: This pooled analysis of pts from 6 MBC trials demonstrates that H-based treatment in MBC is associated with a low incidence of symptomatic CHF (1.6%) and LVEF declines (11-13% of pts). Although CRDs were observed with H, the majority were of limited clinical significance. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6136.