Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with breast cancer treated with HER2 blockade.

PURPOSE: The association between human epidermal growth factor receptor-2 (HER2) blockades and risk of fatal adverse events (FAEs) has not been well described. We carried out a meta-analysis regarding this issue.

METHODS: An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of anti-HER2 therapies on cancer patients. Only randomized controlled trials were included. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR) of FAEs due to the use of HER2 blockades.

RESULTS: Twenty two trials were included. The incidence of FAEs related to HER2 blockades was 0.34%, and there was no statistically significant increase in the risk of FAEs for HER2 blockades versus control in overall population (RR = 1.16, 95%CI: 0.78-1.73). Furthermore, when we performed several subgroup analyses according to drug type (trastuzumab, lapatinib, and pertuzumab), treatment strategy (dual HER2 blockade vs. mono HER2 therapy), and study setting (adjuvant trials vs. metastatic trials), we did not observe any significant differences among the groups. No evidence of publication bias was observed.

CONCLUSION: Compared with control, the addition of HER2 blockades may not increase the risk of FAEs among patients with breast cancer.