The role of ethnicity in personalized dosing of small molecule tyrosine kinase inhibitors used in oncology

Inter-ethnic differences in systemic exposure, efficacy and safety have been reported for some small molecule tyrosine kinase inhibitors (smTKIs). This variability in response related to ethnicity is due to a complex interplay of intrinsic and extrinsic factors that differ between people of different geographic ancestries, influencing the pharmacokinetics and pharmacodynamics of smTKIs. An example of intrinsic factor differences is the higher prevalence of epidermal-growth-factor receptor activating mutations in East Asians compared to Europeans with non-small cell lung cancer (NSCLC), which has been associated with significantly superior survival outcomes with erlotinib and gefitinib. A further example is the inter-ethnic difference reported in the susceptibility to erlotinib-induced adverse-events, which has been correlated to ethnic differences in the expression and activity of CYP3A5 as well as in P-glycoprotein and BCRP mediated transport. Differences in extrinsic factors, including tobacco smoking and complementary medicine use, may contribute to inter-ethnic differences in erlotinib treatment outcomes. Understanding the nature and mechanism of these inter-ethnic differences in smTKIs can help to guide treatment decisions to individualize treatments and improve patient outcomes.