Risk of selected gastrointestinal toxicities in breast cancer patients treated with regimens containing lapatinib; a pooled analysis of randomized controlled studies

We performed a pooled analysis of randomized controlled studies evaluating selected gastrointestinal adverse events associated with lapatinib use in breast cancer patients. Eligible studies included randomized Phase II and III trials of patients with breast cancer on lapatinib; describing events of diarrhea, nausea, vomiting and stomatitis. Our search strategy yielded 390 potentially relevant citations on lapatinib from Pubmed/Medline and other databases. After exclusion of ineligible studies, a total of 19 clinical trials were considered eligible for the analysis. The relative risk (RR) of all-grade diarrhea, nausea, vomiting and stomatitis were 3.09 (95% CI: 2.14-4.43; p < 0.00001), 1.24 (95% CI: 1.07-1.43; p < 0.005), 1.35 (95% CI: 1.22-1.49; p = 0.0001), 1.96 (95% CI: 1.07-2.67; p = 0.02); respectively. Exploratory subgroup analysis showed no effect of disease stage on the RR of the relevant adverse events. While, The RR of high-grade diarrhea, nausea, vomiting and stomatitis were 6.63 (95% CI: 2.94-14.96; p < 0.00001), 1.37 (95% CI: 0.91-2.06; p = 0.13), 1.80 (95% CI: 1.21-2.68; p = 0.004), 2.44 (95% CI: 1.41-4.22 p < 0.001); respectively. Our pooled analysis has demonstrated that regimens containing lapatinib are associated with a significantly increased risk of high-grade diarrhea, vomiting and stomatitis in patients with breast cancer. Clinicians should be aware of these risks and perform regular clinical monitoring.