Does the use of lapatinib increase the risk of fatigue and hepatic toxicities in patients with solid tumors? A critical literature review and meta-analysis

Objective: A systematic review and meta-analysis of fatigue and hepatic adverse events associated with lapatinib use in solid tumor patients were performed. Research design and methods: Eligible studies included randomized Phase II and III trials of patients with solid tumors taking lapatinib. They described events of fatigue, elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. Our search yielded 380 potentially relevant citations on lapatinib from PubMed/Medline, CENTRAL Cochrane registry and ASCO meeting library. Results: After exclusion of ineligible studies, a total of 15 clinical trials were included in the meta-analysis. The relative risk (RR) of all-grade fatigue, elevated ALT, AST and total bilirubin were 0.99 (95% CI 0.87 – 1.13; p = 0.87), 1.12 (95% CI 0.87 – 1.44; p = 0.55), 0.79 (95% CI 0.43 – 1.45; p = 0.44), 5.17 (95% CI 0.18 – 149.81; p = 0.34), respectively. Exploratory subgroup analysis showed no effect of comparator regimen on the RR of the relevant adverse events. Conclusions: This meta-analysis demonstrated that the evidence for a true increased risk of hepatotoxicity or fatigue with lapatinib-based treatment compared to control is not yet fully convincing. Future studies should investigate this risk further. Clinicians must be aware of these risks and perform regular clinical monitoring.