Factors Affecting the Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer

Abstract

To the Editor We read with great interest the article by Chu et al 1 that describes the association of proton pump inhibitors and capecitabine efficacy in advanced gastroesophageal cancer. We agree with the authors that there are limitations to the study. Furthermore, together in viewing the previous publication regarding the same population, 2 we believe that the study raised an issue regarding the difference in response to treatment with anti-human epidermal growth factor receptor 2 (HER2) drugs among cancer patients of different ethnic groups.The differences of ERBB2/HER2 overexpression and related disease prevalence among different ethnic groups are well recognized. However, whether there are difference in response to drug treatment with anti-HER2 agents among different ethnic groups has been controversial. [3][4][5] While data from 2 studies seemingly suggest differences in response to treatment with anti-HER2 agents among ethnic groups, 3,4 data from Li et al 5 recently suggest that trastuzumab emtansine pharmacokinetics are comparable across ethnic groups and that use of the current dosing regimen is appropriate across ethnicities. By examining the publications on the usage of anti-HER2 agents, including trastuzumab, lapatinib, trastuzumab, and pertuzumab, we found that lapatinib is only the drug now showing ethnic differences with seemingly convincing data. 1,2 The question is why only lapatinib, or only lapatinib for patients with gastroesophageal cancer? The answer perhaps should begin with the differences among the anti-HER2 agents. Although these agents are targeting HER2, their mechanisms are different. For example, both trastuzumab and pertuzumab are monoclonal antibodies. However, trastuzumab is a monoclonal antibody that targets subdomain IV of HER2, while pertuzumab inhibits the dimerization of HER2 with other HER receptors. On the other hand, lapatinib is a dual tyrosine kinase inhibitor compound that interrupts the HER2/neu and epidermal growth factor receptor pathways. Furthermore, different cancer types have their different mechanisms in the environment of the genomic backgrounds of different ethnic groups. Although more than 99% of our human genome among different ethnic groups is the same, the small different portion may play the key role for such a difference in responding to drug treatment.Racial difference is always a complicated issue but should not be ignored. We look forward to examining future solid data including subgroup analyses and the genomic accountabilities for the differences.