Neutropenia management with palbociclib in Japanese patients with advanced breast cancer

Breast Cancer. 2019 Sep;26(5):637-650. doi: 10.1007/s12282-019-00970-7. Epub 2019 May 24.


Background: The cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib, in combination with endocrine therapy (ET), significantly prolonged progression-free survival in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC) in PALOMA-2 and PALOMA-3. Neutropenia and palbociclib dose reductions/interruptions occurred more frequently in the Japanese versus overall populations. We evaluated neutropenia patterns, palbociclib dose management, and clinical responses after dose reduction in Japanese patients in PALOMA-2 and PALOMA-3 and a single-arm Japanese phase 2 study.

Methods: PALOMA-2 and the Japanese phase 2 study enrolled postmenopausal women with estrogen receptor-positive, HER2- ABC who had not received prior systemic therapy for advanced disease; PALOMA-3 enrolled women with HR+/HER2- ABC, regardless of menopausal status, whose disease had progressed after prior ET. Palbociclib (125 mg/day) was administered 3 weeks on/1 week off. Dose reduction/interruption, cycle delay, tumor response, and laboratory-assessed neutropenia were analyzed in Japanese patients who received palbociclib.

Results: A total of 101 Japanese patients received palbociclib + ET. Among Japanese patients in the 3 studies, the frequency of all-grade/grade 3/grade 4 neutropenia was 94%/53%/34%, 100%/69%/21%, and 100%/67%/26%, respectively. Twenty (63%), 28 (67%), and 15 (56%) patients required palbociclib dose reduction. Dose interruption or reduction did not affect palbociclib treatment duration, and durable tumor response was observed despite dose reduction.

Conclusion: Neutropenia was manageable with dose modifications, without affecting palbociclib treatment duration or efficacy.

Trial registration: Pfizer (NCT01740427, NCT01684215, NCT01942135).

Keywords: Advanced breast cancer; Cyclin-dependent kinase; Japanese patients; Neutropenia; Palbociclib.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Hormone Replacement Therapy
  • Humans
  • Japan
  • Menopause
  • Middle Aged
  • Neutropenia / complications
  • Neutropenia / drug therapy*
  • Neutrophils / metabolism
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / administration & dosage
  • Pyridines / therapeutic use*
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Treatment Outcome


  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • palbociclib

Associated data