Early treatment-related neutropenia predicts response to palbociclib

Br J Cancer. 2020 Sep;123(6):912-918. doi: 10.1038/s41416-020-0967-7. Epub 2020 Jul 9.


Background: Palbociclib is highly active in oestrogen-receptor positive (ER+) metastatic breast cancer, but neutropenia is dose limiting. The goal of this study was to determine whether early neutropenia is associated with disease response to single-agent palbociclib.

Methods: Blood count and disease-response data were analysed from two Phase 2 clinical trials at different institutions using single-agent palbociclib: advanced solid tumours positive for retinoblastoma protein and advanced liposarcoma. The primary endpoint was PFS. The primary exposure variable was the nadir absolute neutrophil count (ANC) during the first two cycles of treatment.

Results: One hundred and ninety-six patients (61 breast, 135 non-breast) were evaluated between the two trials. Development of any grade neutropenia was significantly associated with longer median PFS in both the breast cancer (HR 0.29, 95% CI 0.11-0.74, p = 0.010) and non-breast cancer (HR 0.57, 95% CI 0.38-0.85, p = 0.006) cohorts. Grade 3-4 neutropenia was significantly associated with prolonged PFS in the non-breast cohort (HR 0.57, 95% CI 0.38-0.85, p = 0.006) but not in the breast cohort (HR 0.87, 95% CI 0.51-1.47, p = 0.596). Multivariate analysis yielded similar results.

Conclusions: Treatment-related neutropenia in the first two cycles was significantly and independently associated with prolonged PFS, suggesting that neutropenia may be a useful pharmacodynamic marker to guide individualised palbociclib dosing.

Clinical trials registration information: Basket Trial: NCT01037790; Sarcoma Trial: NCT01209598.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / mortality
  • Neutropenia / chemically induced*
  • Piperazines / adverse effects*
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / adverse effects*
  • Pyridines / adverse effects*
  • Young Adult


  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib

Associated data

  • ClinicalTrials.gov/NCT01209598
  • ClinicalTrials.gov/NCT01037790