Personalizing pertuzumab and trastuzumab dosing regimens for adjuvant treatment of HER2-positive breast cancer / 中国临床药理学与治疗学

ABSTRACT

AIM: To design and implement personalized dosing regimens of trastuzumab and pertuzumab for an Asian patient with early breast cancer. METHODS: Trastuzumab and pertuzumab are important therapeutics for patients with HER2-positive breast cancer. Despite the similar pharmacokinetics (PK), their recommended dosing regimens differ pertuzumab dosing is fixed whereas trastuzumab dosing depends on body weight; the dosing frequency is once every three weeks for pertuzumab but includes both once every week (QW) and once every three weeks (Q3W) for trastuzumab. A practicing physician has limited choices for dosing regimens when using the drugs in combination with chemotherapies. Besides convenience in drug administration, efficacy and safety as responses to the drug must be examined as part of studying dose-exposure-response relationship, which is the basis for deciding a dosing regimen. To understand the dose-exposure-response relationship of an individual patient, we reviewed literature on population PK analyses. The associated PK-covariate relationships including influential covariates such as disease status and demographics (e.g., body weight) that informed the patient's underlying dose-exposure-response relationships. Safety and efficacy factors essential for choosing appropriate dosing regimens were also considered - minimal target concentrations, higher adverse event rates in Asian patients, as well as administration convenience. RESULTS:Based on a thorough review of population PK and PK-covariate relationships of pertuzumab and trastuzumab, an individualized dosing regimen of once every two weeks (Q2W) was selected as the treatment option and implemented for this patient. CONCLUSION: The design of an individualized dosing regimen requires the knowledge of individualized dose-exposure-response relationships, and population analysis is an ideal tool for understanding the individualized dose-exposure-response relationships.