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Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials

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 ov...

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Autores principales: Shao, Fengping, Liu, Jun, Duan, Yaoyun, Li, Li, Liu, Liqun, Zhang, Cai, He, Shanyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080644/
https://www.ncbi.nlm.nih.gov/pubmed/32096544
http://dx.doi.org/10.1042/BSR20192226
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author Shao, Fengping
Liu, Jun
Duan, Yaoyun
Li, Li
Liu, Liqun
Zhang, Cai
He, Shanyang
author_facet Shao, Fengping
Liu, Jun
Duan, Yaoyun
Li, Li
Liu, Liqun
Zhang, Cai
He, Shanyang
author_sort Shao, Fengping
collection PubMed
description 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.
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spelling pubmed-70806442020-03-23 Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials Shao, Fengping Liu, Jun Duan, Yaoyun Li, Li Liu, Liqun Zhang, Cai He, Shanyang Biosci Rep Cancer 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. Portland Press Ltd. 2020-03-18 /pmc/articles/PMC7080644/ /pubmed/32096544 http://dx.doi.org/10.1042/BSR20192226 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
spellingShingle Cancer
Shao, Fengping
Liu, Jun
Duan, Yaoyun
Li, Li
Liu, Liqun
Zhang, Cai
He, Shanyang
Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials
title Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials
title_full Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials
title_fullStr Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials
title_full_unstemmed Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials
title_short Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials
title_sort efficacy and safety of parp inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials
topic Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080644/
https://www.ncbi.nlm.nih.gov/pubmed/32096544
http://dx.doi.org/10.1042/BSR20192226
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