PMID- 32581595
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220415
IS  - 1179-1322 (Print)
IS  - 1179-1322 (Electronic)
IS  - 1179-1322 (Linking)
VI  - 12
DP  - 2020
TI  - Efficacy and Safety of Cyclin-Dependent Kinases 4 and 6 Inhibitors in HR+/HER2- 
      Advanced Breast Cancer.
PG  - 4241-4250
LID - 10.2147/CMAR.S254365 [doi]
AB  - PURPOSE: To assess the efficacy and safety of cyclin-dependent kinases 4 and 6 
      inhibitors (CDKi) combined with endocrine therapy (ET) in women with hormone 
      receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative 
      advanced breast cancer (ABC) and compare the efficacy of different CDKi 
      (palbociclib, ribociclib, or abemaciclib). MATERIALS AND METHODS: This study 
      based on randomized Phase 2 or 3 trials of CDKi plus ET compared with placebo 
      plus ET for women with HR+/HER2-ABC and identify relevant randomized clinical 
      trials (RCTs) published prior to February 2020. The primary endpoint was 
      progression-free survival (PFS), the secondary endpoints included overall 
      survival (OS), objective response rate (ORR), clinical benefit response (CBR) and 
      safety. The PROSPERO registry number is 42018081105. RESULTS: The results from 
      eight trials including 4580 participants were pooled. Evidence indicated that the 
      PFS of CDKi group was significantly prolonged (hazard ratio [HR] 0.55, 95% 
      confidence interval [CI] 0.50-0.60, P < 0.01) compared with placebo group. The 
      ORR and CBR were better (risk ratio [RR] 1.47, 95% CI 1.30-1.67, P < 0.01; 1.24, 
      95% CI 1.15-1.35, P < 0.01) in the CDKi group. The OS of CDKi group (HR 0.75, 95% 
      CI 0.67-0.85, P < 0.01) was significantly longer than ET alone. Subgroup analyses 
      confirmed that the benefit was consistent across most subgroups. Subgroup 
      analyses showed no statistically significant difference of PFS among three CDKi: 
      palbociclib vs ribociclib (HR 0.55, 95% CI 0.49-0.60, P = 0.34), palbociclib vs 
      abemaciclib (HR 0.53, 95% CI, 0.47-0.59, P = 0.61), and ribociclib vs abemaciclib 
      (HR 0.56, 95% CI, 0.51-0.62, P = 0.72). Treatment-related grade 3 or 4 
      hematologic adverse events (AEs) were more frequently in CDKi group. CONCLUSION: 
      CDKi combined with ET can significantly prolong PFS and improve the ORR, CBR and 
      OS in patients with HR+/HER2- ABC. However, the advantage of different CDKi has 
      not been established.
CI  - (c) 2020 Xie et al.
FAU - Xie, Ning
AU  - Xie N
AD  - Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics 
      and Gene Regulation, Guangzhou, People's Republic of China.
FAU - Qin, Tao
AU  - Qin T
AD  - Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics 
      and Gene Regulation, Guangzhou, People's Republic of China.
FAU - Ren, Wei
AU  - Ren W
AD  - Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics 
      and Gene Regulation, Guangzhou, People's Republic of China.
FAU - Yao, Herui
AU  - Yao H
AD  - Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics 
      and Gene Regulation, Guangzhou, People's Republic of China.
AD  - Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 
      Guangzhou, People's Republic of China.
FAU - Yu, Yunfang
AU  - Yu Y
AD  - Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics 
      and Gene Regulation, Guangzhou, People's Republic of China.
FAU - Hong, Huangming
AU  - Hong H
AUID- ORCID: 0000-0002-0803-1077
AD  - Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics 
      and Gene Regulation, Guangzhou, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20200604
PL  - New Zealand
TA  - Cancer Manag Res
JT  - Cancer management and research
JID - 101512700
PMC - PMC7280088
OTO - NOTNLM
OT  - CDK4/6 inhibitor
OT  - HER2-negative
OT  - HR-positive
OT  - advanced breast cancer
COIS- The authors report no conflicts of interest in this work.
EDAT- 2020/06/26 06:00
MHDA- 2020/06/26 06:01
PMCR- 2020/06/04
CRDT- 2020/06/26 06:00
PHST- 2020/03/18 00:00 [received]
PHST- 2020/04/30 00:00 [accepted]
PHST- 2020/06/26 06:00 [entrez]
PHST- 2020/06/26 06:00 [pubmed]
PHST- 2020/06/26 06:01 [medline]
PHST- 2020/06/04 00:00 [pmc-release]
AID - 254365 [pii]
AID - 10.2147/CMAR.S254365 [doi]
PST - epublish
SO  - Cancer Manag Res. 2020 Jun 4;12:4241-4250. doi: 10.2147/CMAR.S254365. eCollection 
      2020.