Is it safe to give anthracyclines concurrently with trastuzumab in neo-adjuvant or metastatic settings for HER2-positive breast cancer? A meta-analysis of randomized controlled trials.

Concurrent use of anthracyclines and trastuzumab used to be avoided in the treatment of HER2-positive breast cancer due to the high risk of cardiac toxicity. However, several newly published studies challenged this view and demonstrated that concomitant use of the two agents significantly improved the clinical outcome without causing additional cardiac toxicity. This meta-analysis summarized available data to investigate the safety and efficacy of concurrent use of anthracyclines and trastuzumab. Eligible studies were identified through several search strategies and assessed for quality. Data were extracted from studies in terms of baseline characteristics and key statistics, which were utilized to calculate pooled effect size. Eight studies were included in the meta-analysis to evaluate the cardiac safety of concurrent use of anthracyclines and trastuzumab. It is demonstrated that concomitant administration was moderately associated with increased risk of cardiac-related adverse events (RR = 1.97, 95% CI 1.49-2.60, P < 0.001) by fixed effect model. In addition, subgroup analysis showed combined use of anthracyclines and trastuzumab significantly increased the likelihood of cardiac toxicity in neo-adjuvant setting (RR = 1.51, 95% CI 1.10-2.07, P = 0.01) as well as in palliative setting (RR = 3.92, 95% CI 2.11-7.27, P < 0.001). Also, we found concurrent treatment as in neo-adjuvant treatment setting slightly increased pCR rate by randomized effect model with the pooled RR being 1.52 (95% CI 1.05-2.20, P = 0.03). Concurrent use of anthracyclines and trastuzumab increased the risk of cardiac toxicity in both neo-adjuvant and metastatic settings, although moderately increased pCR rate as neo-adjuvant treatment.