Cardiotoxicity of trastuzumab given for 12 months compared to shorter treatment periods: a systematic review and meta-analysis of six clinical trials
Daniel Eiger, Maria Alice Franzoi, Noam Pondé, Mariana Brandão, Claudia De Angelis, Melanie Schmitt Nogueira, Quentin de Hemptinne, Evandro de Azambuja
Abstract
BACKGROUND: Treatment de-escalation in early-stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has been attempted in order to decrease costs and toxicities. One of the strategies pursued is decreasing trastuzumab treatment duration, with mixed results thus far. Trastuzumab-associated cardiotoxicity, however, may be more frequent with 12 months of trastuzumab compared with shorter treatment lengths. Therefore, we have conducted a meta-analysis to address this question. MATERIALS AND METHODS: A meta-analysis of trials testing 12 months of adjuvant trastuzumab versus shorter regimens, reporting cardiac outcomes in patients with HER2-positive BC was performed with the random effects model with inverse variance weighting. RESULTS: =78.8%) for premature trastuzumab discontinuation due to cardiotoxicity for 12 months versus shorter trastuzumab regimens. Funnel plot analyses indicated a low risk of publication bias. CONCLUSIONS: Compared to shorter treatment durations, there is sufficient evidence that 12 months of trastuzumab yields higher odds for the occurrence of relevant cardiac events. An individual patient-level data meta-analysis is needed in order to provide adequate data on risk factors for cardiotoxicity.