PMID- 34271289
OWN - NLM
STAT- MEDLINE
DCOM- 20211015
LR  - 20211015
IS  - 1532-3080 (Electronic)
IS  - 0960-9776 (Print)
IS  - 0960-9776 (Linking)
VI  - 59
DP  - 2021 Oct
TI  - Adjuvant CDK4/6 inhibitors combined with endocrine therapy in HR-positive, 
      HER2-negative early breast cancer: A meta-analysis of randomized clinical trials.
PG  - 165-175
LID - S0960-9776(21)00410-0 [pii]
LID - 10.1016/j.breast.2021.07.002 [doi]
AB  - BACKGROUND: The benefit of adjuvant cyclin-dependent kinase 4 and 6 (CDK4/6) 
      inhibitors with endocrine therapy (ET) in hormone receptor-positive, human 
      epidermal growth factor 2 receptor-negative (HR+/HER2-) early breast cancer (EBC) 
      is uncertain. Hence, we performed a meta-analysis to determine the efficacy and 
      safety of adjuvant CDK4/6 inhibitors plus ET and to identify potential preferred 
      subpopulations for this regimen. METHODS: A literature search was conducted in 
      PubMed, Embase, Cochrane databases up to Jan 15, 2021. Hazard ratios (HRs) for 
      invasive disease-free survival (IDFS) and risk ratios (RRs) for grade 3/4 adverse 
      events (AEs) and treatment discontinuation were extracted. Analysis with 
      predefined subgroup variables was done. Trial sequential analysis (TSA) was 
      performed to assess the conclusiveness of survival outcomes. RESULTS: Three 
      trials were eligible (N = 12647). Compared with ET, adjuvant CDK4/6 inhibitors 
      with ET prolonged IDFS in patients with HR+/HER2- EBC (HR 0.87, 95% CI 0.76-0.98, 
      p = 0.03, I(2) = 19%), with positive therapeutic responses observed in patients 
      with N2/N3 nodal status (HR 0.83, 95% CI 0.71-0.97, p = 0.02, I(2) = 0%). None of 
      the cumulative z-curves crossed the trial monitoring boundaries in TSA, and no 
      reliable conclusion could be drawn. The combination treatment carried a higher 
      risk of grade 3/4 AEs (RR 4.14, 95% CI 3.33-5.15, p < 0.00001) and an increase in 
      treatment discontinuation due to AEs (RR 19.16, 95% CI 9.27-39.61, p < 0.00001). 
      CONCLUSIONS: Adjuvant CDK4/6 inhibitors with ET might provide survival benefit in 
      HR+/HER2- EBC. A statistically significantly improved IDFS was only observed in 
      N2/N3 subgroup. However, overall evidence favoring the use of this combination 
      regimen was inadequate.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Gao, Hong-Fei
AU  - Gao HF
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China.
FAU - Lin, Ying-Yi
AU  - Lin YY
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China; Shantou University Medical 
      College, Shantou, 515041, Guangdong, China.
FAU - Zhu, Teng
AU  - Zhu T
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China.
FAU - Ji, Fei
AU  - Ji F
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China.
FAU - Zhang, Liu-Lu
AU  - Zhang LL
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China.
FAU - Yang, Ci-Qiu
AU  - Yang CQ
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China.
FAU - Yang, Mei
AU  - Yang M
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China.
FAU - Li, Jie-Qing
AU  - Li JQ
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China.
FAU - Cheng, Min-Yi
AU  - Cheng MY
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China.
FAU - Wang, Kun
AU  - Wang K
AD  - Department of Breast Cancer, Cancer Center, Guangdong Provincial People's 
      Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu 
      District, Guangzhou, 510080, Guangdong, China; Shantou University Medical 
      College, Shantou, 515041, Guangdong, China. Electronic address: 
      gzwangkun@126.com.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
DEP - 20210706
PL  - Netherlands
TA  - Breast
JT  - Breast (Edinburgh, Scotland)
JID - 9213011
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - *Breast Neoplasms/drug therapy
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinase 6
MH  - Female
MH  - Humans
MH  - Protein Kinase Inhibitors/adverse effects
MH  - Randomized Controlled Trials as Topic
MH  - Receptor, ErbB-2
MH  - Receptors, Estrogen
PMC - PMC8287214
OTO - NOTNLM
OT  - Adjuvant
OT  - CDK4/6 inhibitors
OT  - Early breast cancer
OT  - Endocrine therapy
OT  - Meta-analysis
COIS- Declaration of competing interest The authors declare that there is no conflict 
      of interest.
EDAT- 2021/07/17 06:00
MHDA- 2021/10/16 06:00
PMCR- 2021/07/06
CRDT- 2021/07/16 20:23
PHST- 2021/04/26 00:00 [received]
PHST- 2021/06/12 00:00 [revised]
PHST- 2021/07/05 00:00 [accepted]
PHST- 2021/07/17 06:00 [pubmed]
PHST- 2021/10/16 06:00 [medline]
PHST- 2021/07/16 20:23 [entrez]
PHST- 2021/07/06 00:00 [pmc-release]
AID - S0960-9776(21)00410-0 [pii]
AID - 10.1016/j.breast.2021.07.002 [doi]
PST - ppublish
SO  - Breast. 2021 Oct;59:165-175. doi: 10.1016/j.breast.2021.07.002. Epub 2021 Jul 6.