Neutropenia management with palbociclib in Japanese patients with advanced breast cancer.

Abstract

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).

• Authors: Norikazu Masuda, Hirofumi Mukai, Kenichi Inoue, Yoshiaki Rai, Shinji Ohno, Yuko Mori, Satoshi Hashigaki, Yasuaki Muramatsu, Yoshiko Umeyama, Hiroji Iwata, Masakazu Toi
• Journal: Breast cancer (Tokyo, Japan) (Breast Cancer) Vol. 26 Issue 5 Pg. 637-650 (09 2019) ISSN: 1880-4233 [Electronic] Japan
• PMID: 31127500 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

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

Topics

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