Binghe Xu1,2, Huiping Li3, Qingyuan Zhang4, Wan Sun5, Yanke Yu6, Wei Li7, Shusen Wang8, Ning Liao9, Peng Shen10, Yuan Liu5, Yaling Huang5,11, Carlos Linn11, Huadong Zhao5,11, John Jiang5, Diane Wang12,13. 1. 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. Xubinghe@medmail.com.cn. 2. 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. Xubinghe@medmail.com.cn. 3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing, China. 4. Harbin Medical University Cancer Hospital, Heilongjiang Province, China. 5. Pfizer Inc, San Diego, CA, USA. 6. Pfizer Inc, New York, NY, USA. 7. The First Hospital of Jilin University, Jilin, China. 8. Sun Yat-Sen University Cancer Center, Guangdong, China. 9. Guangdong General Hospital, Guangdong, China. 10. The First Affiliated Hospital of College of Medicine, Zhejiang University, Zhejiang, China. 11. Pfizer (China) R&D Co., Ltd, Shanghai, China. 12. Pfizer Inc, San Diego, CA, USA. Diane.Wang@Pfizer.com. 13. Clinical Pharmacology, Global Product Development, Pfizer Inc, 10555 Science Center Dr, San Diego, CA, 92121, USA. Diane.Wang@Pfizer.com.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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, AUCτ was 1217 and 2501 ng∙h/mL, and t½ 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: NCT02499146.
PURPOSE: 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/humanepidermal growth factor receptor 2-negative advanced breast cancer (ABC) in postmenopausal Chinese women to support palbociclib approval in China. METHODS: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. RESULTS: 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, AUCτ was 1217 and 2501 ng∙h/mL, and t½ 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: NCT02499146.
Entities:
Keywords:
Chinese; Metastatic breast cancer; Palbociclib; Pharmacodynamics; Pharmacokinetics
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