Palbociclib plus letrozole versus placebo plus letrozole in Asian postmenopausal women with oestrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Primary results from PALOMA-4.

Abstract

BACKGROUND:

The cyclin-dependent kinase 4/6 inhibitor palbociclib has demonstrated efficacy and a manageable safety profile in combination with endocrine therapy in women with oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in international phase 3 trials. The phase 3 PALOMA-4 trial evaluated the efficacy and safety of palbociclib plus letrozole versus placebo plus letrozole in Asian women with ER+/HER2- ABC.

METHODS:

Postmenopausal women (n = 340) with no prior systemic treatment for advanced disease were randomised 1:1 to palbociclib (125 mg/d orally; 3 weeks on, 1 week off) plus letrozole (2.5 mg/d orally; continuously) or placebo plus letrozole. The primary end-point was investigator-assessed progression-free survival (PFS). Secondary end-points included tumour response and safety.

RESULTS:

Median (95% CI) PFS was 21.5 (16.6-24.9) months with palbociclib plus letrozole and 13.9 (13.7-16.6) months with placebo plus letrozole (hazard ratio, 0.68 [95% CI, 0.53-0.87]; P = 0.0012). Consistent with the established safety profile, the most common adverse events (AEs) with palbociclib plus letrozole were neutropenia, leukopenia, thrombocytopaenia, and anaemia. Grade 3/4 neutropenia was reported in 84.5% of patients in the palbociclib arm versus 1.2% in the placebo arm. One serious AE of febrile neutropenia in the palbociclib group was reported.

CONCLUSIONS:

Findings from PALOMA-4 support the efficacy and safety of first-line palbociclib plus letrozole in postmenopausal Asian women with ER+/HER2- ABC. No new safety concerns of palbociclib plus letrozole were identified.

TRIAL REGISTRATION:

Clinicaltrials. gov, NCT02297438.

• Authors: Binghe Xu, Xichun Hu, Wei Li, Tao Sun, Kunwei Shen, Shusen Wang, Ying Cheng, Qingyuan Zhang, Shude Cui, Zhongsheng Tong, Cuizhi Geng, Erwei Song, Chiun-Sheng Huang, Virote Sriuranpong, Roger K C Ngan, Yee H Chia, Xinwei Wang, Huadong Zhao
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 175 Pg. 236-245 (11 2022) ISSN: 1879-0852 [Electronic] England
• PMID: 36155117 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Piperazines
• Pyridines
• Receptors, Estrogen
• Letrozole
• ERBB2 protein, human
• Receptor, ErbB-2
• Cyclin-Dependent Kinase 4
• palbociclib

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (pathology)
• Cyclin-Dependent Kinase 4
• Female
• Humans
• Letrozole
• Neutropenia (drug therapy)
• Piperazines
• Postmenopause
• Pyridines
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)