HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity: a systematic review and meta-analysis

Associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity have been reported. To consolidate the results from all available reports in scientific databases, systematic review and meta-analysis techniques were used to quantify these associations. Studies investigating associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity were systematically searched in PubMed, Human Genome Epidemiology Network, and the Cochrane Library. Primary outcomes were the associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity. Overall odds ratios (ORs) with the corresponding 95%CIs were calculated using a random-effect model to determine the associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity. A clear association between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity was identified in our analyses. The summary OR was 6.23 (95%CI = 4.11-9.45). Similar associations were also found in the subgroup analyses by lapatinib treatment regimens. ORs were 10.04 (95%CI = 6.15-16.39), 8.65 (95%CI = 4.52-16.58), and 3.88 (95%CI = 2.20-6.82) in the lapatinib group, lapatinib + trastuzumab group, and lapatinib + chemotherapy or lapatinib + trastuzumab + chemotherapy group, respectively. Since HLA-DRB1*07:01 is associated with lapatinib-induced hepatotoxicity, genetic screening of HLA-DRB1*07:01 in breast cancer patients prior to lapatinib therapy is warranted for patient safety. In addition, further studies should define the risk of HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity in specific ethnicities.