RESUMEN
Treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2; HER2-low) has drawn much attention in recent years. With the proven therapeutic effect of trastuzumab deruxtecan (T-DXd) in patients with HER2-low (immunohistochemistry [IHC] 1+, or IHC2+/in situ hybridization [ISH]-) breast cancer, HER2-low may become a new subtype of targeted therapy for breast cancer. The expert committee formulated this consensus based on the current clinical studies and clinical medication experience. The current consensus is the collaborative work of an interdisciplinary working group, including experts in the fields of pathology and oncology. The purpose of this consensus was to guide the clinical diagnosis and treatment of HER2-low breast cancer, thereby prolonging the overall survival of patients.
RESUMEN
BACKGROUND: Pharmacokinetics of vinorelbine is mainly known from studies conducted in European patients. Interethnic differences in drug disposition may, however, induce interethnic variation in drug exposure. This paper aimed to evaluate the effect of ethnicity on the bioavailability and clearance of oral and intravenous vinorelbine. METHODS: Oral and intravenous vinorelbine pharmacokinetics data in Asian patients were pooled from two-phase II studies of patients with non-small-cell lung cancer or advanced breast cancer in China. Blood vinorelbine and its active metabolite, 4'-O-deacetylvinorelbine, were quantified using liquid chromatography-tandem mass spectrometry. Bayesian pharmacokinetic parameters were calculated and vinorelbine monotherapy results (intravenous 25 mg/m2; oral 60 mg/m2) of the Asian data set were compared to a reference European data set (intravenous 30 mg/m2; oral 80 mg/m2). Subsequently, a population pharmacokinetics analysis was conducted in a combined cohort (Asian data set + historical vinorelbine pharmacokinetics database) to investigate for a potential effect of ethnicity. RESULTS: Pharmacokinetics data from the Asian data set (oral: n = 47; intravenous: n = 34) was compared to the European reference data set (oral: n = 48; intravenous: n = 48). Mean apparent clearance of oral vinorelbine and mean absolute clearance of intravenous vinorelbine was comparable between the Asian and reference European data set. A population pharmacokinetic analysis (oral: n = 222; intravenous: n = 111) demonstrated no influence of ethnicity on oral and intravenous vinorelbine bioavailability and clearance. CONCLUSION: Vinorelbine pharmacokinetics were found to be comparable between Asian and European patients. No relevant influence of ethnicity on vinorelbine bioavailability and clearance for oral and intravenous routes of administration was observed.