No Increased Cardiac Toxicity with Dual HER2 Blockade Therapy for Breast Cancer

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CHICAGO—Combined anti-HER2 therapy, with or without chemotherapy, does not increase the risk for cardiac toxicities compared to anti-HER2 monotherapy, according to a meta-analysis of randomized trials presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

After searching Medline, the Cochrane library, and electronic abstract databases of the major international congresses', six randomized trials that evaluated administration of anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination therapy were determined to have met the outcomes for this analysis: congestive heart failure (CHF) grade 3 or higher and left ventricular ejection fraction (LVEF) decline less than 50%, or more than 10% from baseline.  

All eligible trials reported data on CHF, and five reported on LVEF.

The investigators calculated pooled odds ratios (ORs) and confidence intervals using the Peto method. Overall incidence of congestive heart failure (CHF) for combined anti-HER2 therapy was 0.88% (95% CI: 0.47%-1.64%) and for anti-HER2 monotherapy, 1.49% (95% CI: 0.98%-2.23%); LVEF decline was 3.1% (95% CI: 2.2%-4.4%) and 2.9% (95% CI: 2.1%-4.1%), respectively.

“In subgroup analyses, there were no significant differences in CHF or LVEF decline among different treatment settings or types of anti-HER2 therapy,” noted Antonis Valachis, MD, of the Department of Oncology Sörmland Mälarsjukhuset, Eskilstuna, Sweden, and colleagues.

For patients with breast cancer receiving dual HER2 blockade versus monotherapy, the pooled odds ratio (OR) for CHF was 0.58 (95% CI: 0.26-1.27; P=0.17); for LVEF, the OR was 0.88 (95% CI: 0.53-1.48; P=0.64).

"The clinical implication of our results is that the combination of dual HER2 blockade is, so far, as safe as anti-HER2 monotherapy in terms of cardiotoxicity,” Dr. Valachis concluded. “As a result, the clinicians who choose such combinations for the treatment of their patients or propose a clinical study to their patients with combination should not be worried about increased cardiac toxicity."

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