PMID- 30897298
OWN - NLM
STAT- MEDLINE
DCOM- 20200507
LR  - 20210109
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 8
IP  - 4
DP  - 2019 Apr
TI  - Safety and efficacy profile of cyclin-dependent kinases 4/6 inhibitor palbociclib 
      in cancer therapy: A meta-analysis of clinical trials.
PG  - 1389-1400
LID - 10.1002/cam4.1970 [doi]
AB  - BACKGROUND: Palbociclib is a small-molecule, cyclin-dependent kinase 4 and 6 
      inhibitor, which prevents phosphorylation of the retinoblastoma (Rb) protein and 
      inhibits cell-cycle progression from G1 to S phase. We performed this 
      meta-analysis to estimate the safety and efficacy of palbociclib in cancer 
      patients from clinical trials. METHODS: PubMed and EMBASE were searched for 
      eligible studies. Adverse events (AE) of grade >/=3 and all-grade (1-5) were 
      extracted to calculate event rates. Odds ratios (ORs) with 95% confidence 
      interval (CI) were calculated to estimate the safety of palbociclib in endocrine 
      treatment-combined studies. A fixed effects model was used when homogeneity was 
      low (I(2)  </= 50%). A random effects model was adopted when there was a 
      significant heterogeneity (I(2)  > 50%). For efficacy endpoints, hazard ratio 
      (HR) and 95% CI for progression-free survival (PFS) or overall survival (OS) were 
      extracted and analyzed. RESULTS: Nine clinical trials representing 1534 patients 
      were identified. The most frequently observed all-grade adverse events (AEs) in 
      patients treated with palbociclib were neutropenia (event rate: 68.1%), 
      leukopenia (51.7%), fatigue (35.9%), anemia (34.7%), and thrombocytopenia 
      (30.9%). The most common grade 3 or more toxicities were neutropenia (51.6%), 
      leukopenia (29.4%), and thrombocytopenia (7.5%). Hematologic adverse events had 
      high occurrence in the palbociclib group. The pooled analysis of survival 
      outcomes suggested that palbociclib produced clinical benefits in breast cancers 
      and Rb-positive tumors. More specifically, palbociclib was associated with 
      significant improvement of PFS (HR: 0.518, 95% CI: 0.444-0.604) in the treatment 
      of ER-positive and HER2-negative breast cancer. CONCLUSIONS: Hematologic adverse 
      events were common in palbociclib-treated cancer patients. Since palbociclib 
      produced a higher PFS rate with a low serious complication rate, it can be a 
      promising novel target therapy drug for treating ER-positive and HER2-negative 
      breast cancer.
CI  - (c) 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Guo, Linghong
AU  - Guo L
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, China.
AD  - West China School of Medicine, Sichuan University, Chengdu, China.
FAU - Hu, Yuanyuan
AU  - Hu Y
AD  - West China School of Medicine, Sichuan University, Chengdu, China.
FAU - Chen, Xi
AU  - Chen X
AD  - West China School of Stomatology, Sichuan University, Chengdu, China.
FAU - Li, Qingfang
AU  - Li Q
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Wei, Benling
AU  - Wei B
AD  - General Hospital of Xuzhou Mining Group, Xuzhou, China.
FAU - Ma, Xuelei
AU  - Ma X
AUID- ORCID: 0000-0002-9148-5001
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20190321
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - G9ZF61LE7G (palbociclib)
SB  - IM
MH  - Clinical Trials as Topic
MH  - Female
MH  - Humans
MH  - Male
MH  - Neoplasms/*drug therapy/mortality
MH  - Odds Ratio
MH  - Piperazines/*adverse effects/therapeutic use
MH  - Protein Kinase Inhibitors/*adverse effects/therapeutic use
MH  - Pyridines/*adverse effects/therapeutic use
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC6488107
OTO - NOTNLM
OT  - CDK 4/6 inhibitor
OT  - efficacy
OT  - meta-analysis
OT  - palbociclib
OT  - safety
COIS- None declared.
EDAT- 2019/03/22 06:00
MHDA- 2020/05/08 06:00
PMCR- 2019/03/21
CRDT- 2019/03/22 06:00
PHST- 2018/08/23 00:00 [received]
PHST- 2018/12/06 00:00 [revised]
PHST- 2018/12/22 00:00 [accepted]
PHST- 2019/03/22 06:00 [pubmed]
PHST- 2020/05/08 06:00 [medline]
PHST- 2019/03/22 06:00 [entrez]
PHST- 2019/03/21 00:00 [pmc-release]
AID - CAM41970 [pii]
AID - 10.1002/cam4.1970 [doi]
PST - ppublish
SO  - Cancer Med. 2019 Apr;8(4):1389-1400. doi: 10.1002/cam4.1970. Epub 2019 Mar 21.