PMID- 32096544
OWN - NLM
STAT- MEDLINE
DCOM- 20210319
LR  - 20210319
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 40
IP  - 3
DP  - 2020 Mar 27
TI  - Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian 
      cancer: a meta-analysis of nine randomized controlled trials.
LID - 10.1042/BSR20192226 [doi]
LID - BSR20192226
AB  - PURPOSE: Poly ADP ribose polymerase (PARP) inhibitors can effectively kill cancer 
      cells by restraining the activity of DNA repair enzymes and utilizing the 
      characteristics of BRCA mutations. This article evaluates the efficacy and safety 
      of PARP inhibitors (PARPis) in the maintenance treatment of ovarian cancer. 
      METHOD: We searched for clinical trials in electronic databases. PARPis efficacy 
      were evaluated by the hazard ratios (HR) and its 95% confidence intervals (95% 
      CI) of overall survival (OS) and progression-free survival (PFS) between the 
      PARPis groups and placebo groups, while the PARPis' safety was assessed by 
      relative risk (RR) values of adverse events (AEs) between the two arms. RESULTS: 
      The immature OS data manifested that patients with BRCA mutation receiving PARPis 
      therapy versus placebo therapy appeared to have longer OS (HR = 0.78, 95%CI = 
      0.61-1.01; P = 0.06). Compared with placebo group, PARP group had a significant 
      advantage in PFS in ovarian cancer patients with BRCA wild-type (BRCAwt), BRCA 
      mutation (BRCAm), BRCA status unclassified, BRCA1 mutation subgroup and the BRCA2 
      mutation subgroup (BRCAwt: HR = 0.53, 95%CI = 0.42-0.68, P < 0.00001; BRCAm: HR = 
      0.30, 95%CI = 0.26-0.34, P < 0.00001; BRCA status unclassified: HR = 0.52, 95%CI 
      = 0.41-0.66, P < 0.00001; BRCA1m: HR = 0.38, 95%CI = 0.29-0.48, P < 0.00001; 
      BRCA2m: HR = 0.23, 95%CI = 0.10-0.57, P = 0.001). Our analysis revealed the 
      incidence rates for AEs of grade >/=3 (grades 3 to 4) and serious AEs in PARPis 
      group were 55.19% and 26.29%, respectively. CONCLUSION: Our meta-analysis 
      demonstrates that PARPis therapy can significantly improve PFS in ovarian cancer 
      patients, but it has no benefit in OS. However, the therapy is associated with a 
      significant increase in the risk of AEs of grade >/= 3 and serious AEs.
CI  - (c) 2020 The Author(s).
FAU - Shao, Fengping
AU  - Shao F
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun 
      Yat-sen University, Zhongshan Second Road 58, Guangzhou 510080, Guangdong, P. R. 
      China.
FAU - Liu, Jun
AU  - Liu J
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun 
      Yat-sen University, Zhongshan Second Road 58, Guangzhou 510080, Guangdong, P. R. 
      China.
FAU - Duan, Yaoyun
AU  - Duan Y
AD  - School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical 
      Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China, 
      518055.
FAU - Li, Li
AU  - Li L
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun 
      Yat-sen University, Zhongshan Second Road 58, Guangzhou 510080, Guangdong, P. R. 
      China.
FAU - Liu, Liqun
AU  - Liu L
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun 
      Yat-sen University, Zhongshan Second Road 58, Guangzhou 510080, Guangdong, P. R. 
      China.
FAU - Zhang, Cai
AU  - Zhang C
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun 
      Yat-sen University, Zhongshan Second Road 58, Guangzhou 510080, Guangdong, P. R. 
      China.
FAU - He, Shanyang
AU  - He S
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun 
      Yat-sen University, Zhongshan Second Road 58, Guangzhou 510080, Guangdong, P. R. 
      China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (BRCA1 Protein)
RN  - 0 (BRCA1 protein, human)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - EC 2.4.2.30 (PARP1 protein, human)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
SB  - IM
MH  - BRCA1 Protein/genetics
MH  - Carcinoma, Ovarian Epithelial/drug therapy/metabolism
MH  - China
MH  - Female
MH  - Humans
MH  - Ovarian Neoplasms/*drug therapy/metabolism
MH  - Poly (ADP-Ribose) Polymerase-1/metabolism
MH  - Poly(ADP-ribose) Polymerase Inhibitors/adverse effects/metabolism/*pharmacology
MH  - Poly(ADP-ribose) Polymerases
MH  - Progression-Free Survival
MH  - Randomized Controlled Trials as Topic
MH  - Survival Analysis
PMC - PMC7080644
OTO - NOTNLM
OT  - Adverse events
OT  - BRCA
OT  - Efficacy and safety
OT  - Ovarian cancer
OT  - PARP inhibitors
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2020/02/26 06:00
MHDA- 2021/03/20 06:00
PMCR- 2020/03/18
CRDT- 2020/02/26 06:00
PHST- 2019/07/11 00:00 [received]
PHST- 2020/01/21 00:00 [revised]
PHST- 2020/02/24 00:00 [accepted]
PHST- 2020/02/26 06:00 [pubmed]
PHST- 2021/03/20 06:00 [medline]
PHST- 2020/02/26 06:00 [entrez]
PHST- 2020/03/18 00:00 [pmc-release]
AID - 222203 [pii]
AID - BSR20192226 [pii]
AID - 10.1042/BSR20192226 [doi]
PST - ppublish
SO  - Biosci Rep. 2020 Mar 27;40(3):BSR20192226. doi: 10.1042/BSR20192226.