National Cancer Center, National Clinical Research Center for Cancer, State Key Laboratory of Molecular Oncology/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Number 17 Pan Jia Yuan Nan Li, Chaoyang District, Beijing, 100021, China.
Cancer Chemother Pharmacol. 2021 Jul;88(1):131-141. doi: 10.1007/s00280-021-04263-9. Epub 2021 Apr 9.
This phase 1, open-label, single-arm clinical trial evaluated pharmacokinetics, safety, and biomarker activity of palbociclib-letrozole as first-line treatment for estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) in postmenopausal Chinese women to support palbociclib approval in China.
Patients received palbociclib 125 mg once daily (3/1 schedule) plus letrozole 2.5 mg once daily. Blood samples were collected predose and ≤ 120 h after single and multiple doses of palbociclib. The incidence and severity of adverse events were reported. Skin biopsy tissues and blood samples were collected for biomarker assessments.
By 31 July 2018, 26 patients were enrolled. After single and multiple dosing, palbociclib maximum plasma concentration was 82.14 and 139.7 ng/mL, apparent clearance was 52.40 and 49.97 L/h, AUC was 1217 and 2501 ng∙h/mL, and t was 23.46 and 27.26 h, respectively. Levels of Ki67, retinoblastoma protein, and thymidine kinase decreased after palbociclib treatment. A similar safety profile as previously reported was observed.
Pharmacokinetic and pharmacodynamic effects of palbociclib were well characterized in Chinese patients with ABC. Despite higher exposure, pharmacokinetic parameters were similar to those of a previously studied non-Asian population. No palbociclib dose adjustment based on Chinese ethnicity is needed. Palbociclib-letrozole had a manageable safety profile.
NCT02499146.
本项Ⅰ期、开放标签、单臂临床试验评估了帕博西尼联合来曲唑作为绝经后中国女性激素受体阳性/人表皮生长因子受体 2 阴性晚期乳腺癌（ABC）一线治疗的药代动力学、安全性和生物标志物活性，以支持帕博西尼在中国的批准。
患者接受帕博西尼 125mg 每日一次（3/1 方案）联合来曲唑 2.5mg 每日一次。在单次和多次给予帕博西尼后，采集用药前和≤120 小时的血样。报告不良事件的发生率和严重程度。采集皮肤活检组织和血样进行生物标志物评估。
截至 2018 年 7 月 31 日，共入组 26 例患者。单次和多次给药后，帕博西尼的最大血浆浓度分别为 82.14 和 139.7ng/mL，表观清除率分别为 52.40 和 49.97L/h，AUC 分别为 1217 和 2501ng·h/mL，t1/2 分别为 23.46 和 27.26h。Ki67、视网膜母细胞瘤蛋白和胸苷激酶水平在帕博西尼治疗后降低。观察到与先前报道相似的安全性特征。
在中国 ABC 患者中，帕博西尼的药代动力学和药效学特征得到了很好的描述。尽管暴露量较高，但药代动力学参数与之前研究的非亚洲人群相似。不需要基于中国人种调整帕博西尼的剂量。帕博西尼联合来曲唑的安全性特征可管理。
NCT02499146。
