To investigate the risk of hepatic toxicity and gastrointestinal events in breast cancer patients treated with neratinib.

The Cochrane, PubMed, Web of Science, CNKI, VIP and Wanfang databases were searched for randomized controlled trials in breast cancer patients treated with neratinib from the earliest data available to March 1, 2018. The enrolled studies described hepatic toxicity such as elevated alanine aminotransferase(ALT) or elevated aspartate aminotransferase(AST) or gastrointestinal events induding diarrhea, vomiting and nausea. All adverse events were divided into 5 grades(1-5). The adverse events at all levels included all 5 grades and high-level adverse events refered to the events at grade 3 and above. Two researchers independently completed literature retrieval and data extraction, and evaluated the quality of the included studies using the recommended bias tools of the Cochrane handbook. The relative risk (RR) and 95% confidence interval (CI) were used as effect quantities and Q test was used to analyze the heterogeneity of the data. A fixed effect model or a random effect model was chosen according to the results of the heterogeneity.

Four studies were included, among which neratinib monotherapy was used in two studies and neratinib combined with paclitaxel in other two studies. The results showed that there was no significant difference in the incidence of ALT and AST increase at all levels between neratinib group and control group (ALT: RR=1.37, 95%CI: 0.50-3.76, P=0.54; AST: RR=1.19, 95%CI: 0.36-3.92, P=0.78). The incidence of high-level elevation of ALT was significantly higher in neratinib group than in control group (RR=3.63, 95%CI: 1.58-8.36, P<0.01), while no significant difference was found in the incidence of high-level elevation of AST (RR=2.08, 95%CI: 0.80-5.43, P=0.13). As to gastrointestinal events, the incidences of nausea at all levels and high level were significantly higher in neratinib group than in control group(at all levels: RR=2.06, 95%CI: 1.38-3.08, P<0.01; high-level: RR=8.77, 95%CI: 2.91-26.40, P<0.01); the incidences of vomiting at all levels and high level were significantly higher in neratinib group than in control group(at all levels: RR=2.13, 95%CI: 1.43-3.18, P<0.01; high-level: RR=6.22, 95%CI: 3.16-12.27, P<0.01). The incidence of nausea at all levels and high level presented no significant difference between neratinib group and control group (at all levels: RR=1.28, 95%CI: 0.81-2.04, P=0.29; high-level: RR=3.10, 95%CI: 0.87-11.00, P=0.08).

The application of neratinib in breast cancer patients will increase the incidences of high-level ALT increase, diarrhea and vomiting, but no significant changes are observed in AST increase and nausea. Therefore, the liver function and gastrointestinal function should be closely monitored if neratinib is used against breast cancer.