Pharmacokinetics, safety, activity, and biomarker analysis of palbociclib plus letrozole as first-line treatment for ER+/HER2- advanced breast cancer in Chinese women

Cancer Chemother Pharmacol. 2021 Jul;88(1):131-141. doi: 10.1007/s00280-021-04263-9. Epub 2021 Apr 9.


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.

Keywords: Chinese; Metastatic breast cancer; Palbociclib; Pharmacodynamics; Pharmacokinetics.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asians
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Female
  • Humans
  • Letrozole / adverse effects
  • Letrozole / pharmacokinetics*
  • Letrozole / therapeutic use*
  • Middle Aged
  • Piperazines / adverse effects
  • Piperazines / pharmacokinetics*
  • Piperazines / therapeutic use*
  • Postmenopause / metabolism
  • Pyridines / adverse effects
  • Pyridines / pharmacokinetics*
  • Pyridines / therapeutic use*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Treatment Outcome


  • Biomarkers, Tumor
  • Piperazines
  • Pyridines
  • Receptors, Estrogen
  • Letrozole
  • Receptor, ErbB-2
  • palbociclib

Associated data