PMID- 36155117
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20221108
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 175
DP  - 2022 Nov
TI  - 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.
PG  - 236-245
LID - S0959-8049(22)00489-0 [pii]
LID - 10.1016/j.ejca.2022.08.012 [doi]
AB  - 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.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Xu, Binghe
AU  - Xu B
AD  - National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and 
      Peking Union Medical College, Beijing, China. Electronic address: 
      xubinghe@medmail.com.cn.
FAU - Hu, Xichun
AU  - Hu X
AD  - Fudan University Shanghai Cancer Center, Shanghai, China.
FAU - Li, Wei
AU  - Li W
AD  - The First Hospital of Jilin University, Changchun, China.
FAU - Sun, Tao
AU  - Sun T
AD  - Cancer Hospital of China Medical University/Liaoning Cancer Hospital, Shenyang, 
      Liaoning, China.
FAU - Shen, Kunwei
AU  - Shen K
AD  - Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 
      Shanghai, China.
FAU - Wang, Shusen
AU  - Wang S
AD  - Sun Yat-Sen University Cancer Center, Guangzhou, China.
FAU - Cheng, Ying
AU  - Cheng Y
AD  - Jilin Provincial Cancer Hospital, Changchun, China.
FAU - Zhang, Qingyuan
AU  - Zhang Q
AD  - Harbin Medical University Cancer Hospital/Oncology Department, Harbin, China.
FAU - Cui, Shude
AU  - Cui S
AD  - Henan Cancer Hospital, Zhengzhou, China.
FAU - Tong, Zhongsheng
AU  - Tong Z
AD  - Tianjin Cancer Hospital/Breast Cancer Department, Tianjin, China.
FAU - Geng, Cuizhi
AU  - Geng C
AD  - Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
FAU - Song, Erwei
AU  - Song E
AD  - Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
FAU - Huang, Chiun-Sheng
AU  - Huang CS
AD  - National Taiwan University Hospital and National Taiwan University College of 
      Medicine, Taipei, Taiwan.
FAU - Sriuranpong, Virote
AU  - Sriuranpong V
AD  - Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial 
      Hospital, Bangkok, Thailand.
FAU - Ngan, Roger K C
AU  - Ngan RKC
AD  - Department of Clinical Oncology, The University of Hong Kong, Hong Kong.
FAU - Chia, Yee H
AU  - Chia YH
AD  - Tan Tock Seng Hospital, Singapore.
FAU - Wang, Xinwei
AU  - Wang X
AD  - Pfizer (China) R&D Co., Ltd., Shanghai, China.
FAU - Zhao, Huadong
AU  - Zhao H
AD  - Pfizer (China) R&D Co., Ltd., Shanghai, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT02297438
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220922
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Estrogen)
RN  - 7LKK855W8I (Letrozole)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - G9ZF61LE7G (palbociclib)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Breast Neoplasms/pathology
MH  - Cyclin-Dependent Kinase 4
MH  - Female
MH  - Humans
MH  - Letrozole
MH  - *Neutropenia/drug therapy
MH  - Piperazines
MH  - Postmenopause
MH  - Pyridines
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen/metabolism
OTO - NOTNLM
OT  - Advanced breast cancer
OT  - Asian
OT  - Letrozole
OT  - Oestrogen receptor-positive
OT  - Palbociclib
COIS- Conflict of interest statement The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Binghe Xu has been an advisor for Novartis and Roche, has received 
      research funding from Hengrui, and has served on speakers bureaus for 
      AstraZeneca, Pfizer Inc, Roche, and Eisai. Chiun-Sheng Huang has been an advisor 
      for Amgen, AstraZeneca, Lilly, Novartis, Pfizer Inc, and Roche; has received 
      research funding from Amgen, AstraZeneca, Daiichi Sankyo, EirGenix, Lilly, MSD, 
      Novartis, OBI, Pfizer, and Roche; and has served on a speakers bureau for Roche. 
      Virote Sriuranpong has received research funding from Roche, MSD, Novartis, 
      Pfizer Inc, and AstraZeneca and has been an advisor for Roche, Novartis, 
      Boehringer Ingelheim, MSD, Pfizer Inc, and Amgen. Roger Kai Cheong Ngan has 
      received research funding from Pfizer Inc; has been an advisor for Pfizer Inc, 
      Novartis, Sanofi, AstraZeneca, Lilly, MSD, Zai Lab, Roche, and Eisai; and has 
      served on speakers bureaus for Novartis, AstraZeneca, Sanofi, Pfizer Inc, Zai 
      Lab, Eisai, Lilly, and MSD. Xinwei Wang is an employee of and has stocks or stock 
      options in Pfizer Inc.Huadong Zhao is an employee of Pfizer Inc.Xichun Hu, Wei 
      Li, Tao Sun, Kunwei Shen, Shusen Wang, Ying Cheng, Qingyuan Zhang, Shude Cui, 
      Zhongsheng Tong, Cuizhi Geng, Erwei Song, and Yee Hong Chia have no conflicts of 
      interest to disclose.
EDAT- 2022/09/27 06:00
MHDA- 2022/10/19 06:00
CRDT- 2022/09/26 15:17
PHST- 2022/04/28 00:00 [received]
PHST- 2022/08/09 00:00 [revised]
PHST- 2022/08/12 00:00 [accepted]
PHST- 2022/09/27 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/09/26 15:17 [entrez]
AID - S0959-8049(22)00489-0 [pii]
AID - 10.1016/j.ejca.2022.08.012 [doi]
PST - ppublish
SO  - Eur J Cancer. 2022 Nov;175:236-245. doi: 10.1016/j.ejca.2022.08.012. Epub 2022 
      Sep 22.