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Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer

Background: The prognostic factors for efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer remain unknown. The purpose of this study is to evaluate the efficacy of PARP inhibitors and to explore their prognostic factors in ovarian cancer. Methods: PubMed, Embase, and conferen...

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Autores principales: Huang, Xuan-zhang, Jia, Han, Xiao, Qiong, Li, Run-zhou, Wang, Xing-shuang, Yin, Hai-yan, Zhou, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308557/
https://www.ncbi.nlm.nih.gov/pubmed/32612955
http://dx.doi.org/10.3389/fonc.2020.00958
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author Huang, Xuan-zhang
Jia, Han
Xiao, Qiong
Li, Run-zhou
Wang, Xing-shuang
Yin, Hai-yan
Zhou, Xin
author_facet Huang, Xuan-zhang
Jia, Han
Xiao, Qiong
Li, Run-zhou
Wang, Xing-shuang
Yin, Hai-yan
Zhou, Xin
author_sort Huang, Xuan-zhang
collection PubMed
description Background: The prognostic factors for efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer remain unknown. The purpose of this study is to evaluate the efficacy of PARP inhibitors and to explore their prognostic factors in ovarian cancer. Methods: PubMed, Embase, and conference databases were searched for relevant prospective clinical trials. The primary outcomes included overall survival (OS), progression-free survival (PFS), and their prognostic factors. Secondary outcomes included PFS2, time to first subsequent therapy (TFST), time to second subsequent therapy (TSST), chemotherapy-free interval (CFI), and their prognostic factors. Hazard ratio (HR) with a 95% confidence interval (CI) was used as an effect measure. Results: PARP inhibitors significantly prolonged PFS in patients with ovarian cancer regardless of their BRCA and HRD status (HR = 0.44, 95% CI = 0.36–0.55). BRCA mutation, HRD-positive status, and sensitivity to platinum represented effective prognostic factors for PFS (P(interaction) < 0.01 and within-trial interaction HR < 1). Other clinicopathological factors did not predict the benefit of PFS (P(interaction) > 0.10). Moreover, PARP inhibitors significantly increased PFS2, TFST, TSST, and CFI, with significant BRCA-related differences. However, HRD-related differences could not be evaluated due to the lack of eligible studies. Furthermore, PARP inhibitors did not translate into prolonged OS, although there was a benefit associated with OS (HR = 0.84, 95% CI = 0.70–1.02). PARP inhibitors used as maintenance therapy after first or subsequent line therapy improved OS (HR = 0.77, 95% CI = 0.63–0.93). Conclusions: PARP inhibitors can significantly prolong PFS, PFS2, TFST, TSST, and CFI in ovarian cancer patients. BRCA mutation, HRD-positive status, and sensitivity to platinum are effective prognostic factors for the efficacy of PARP inhibitors. However, despite the PFS improvement, this does not translate into prolonged OS for patients.
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spelling pubmed-73085572020-06-30 Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer Huang, Xuan-zhang Jia, Han Xiao, Qiong Li, Run-zhou Wang, Xing-shuang Yin, Hai-yan Zhou, Xin Front Oncol Oncology Background: The prognostic factors for efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer remain unknown. The purpose of this study is to evaluate the efficacy of PARP inhibitors and to explore their prognostic factors in ovarian cancer. Methods: PubMed, Embase, and conference databases were searched for relevant prospective clinical trials. The primary outcomes included overall survival (OS), progression-free survival (PFS), and their prognostic factors. Secondary outcomes included PFS2, time to first subsequent therapy (TFST), time to second subsequent therapy (TSST), chemotherapy-free interval (CFI), and their prognostic factors. Hazard ratio (HR) with a 95% confidence interval (CI) was used as an effect measure. Results: PARP inhibitors significantly prolonged PFS in patients with ovarian cancer regardless of their BRCA and HRD status (HR = 0.44, 95% CI = 0.36–0.55). BRCA mutation, HRD-positive status, and sensitivity to platinum represented effective prognostic factors for PFS (P(interaction) < 0.01 and within-trial interaction HR < 1). Other clinicopathological factors did not predict the benefit of PFS (P(interaction) > 0.10). Moreover, PARP inhibitors significantly increased PFS2, TFST, TSST, and CFI, with significant BRCA-related differences. However, HRD-related differences could not be evaluated due to the lack of eligible studies. Furthermore, PARP inhibitors did not translate into prolonged OS, although there was a benefit associated with OS (HR = 0.84, 95% CI = 0.70–1.02). PARP inhibitors used as maintenance therapy after first or subsequent line therapy improved OS (HR = 0.77, 95% CI = 0.63–0.93). Conclusions: PARP inhibitors can significantly prolong PFS, PFS2, TFST, TSST, and CFI in ovarian cancer patients. BRCA mutation, HRD-positive status, and sensitivity to platinum are effective prognostic factors for the efficacy of PARP inhibitors. However, despite the PFS improvement, this does not translate into prolonged OS for patients. Frontiers Media S.A. 2020-06-16 /pmc/articles/PMC7308557/ /pubmed/32612955 http://dx.doi.org/10.3389/fonc.2020.00958 Text en Copyright © 2020 Huang, Jia, Xiao, Li, Wang, Yin and Zhou. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Huang, Xuan-zhang
Jia, Han
Xiao, Qiong
Li, Run-zhou
Wang, Xing-shuang
Yin, Hai-yan
Zhou, Xin
Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer
title Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer
title_full Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer
title_fullStr Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer
title_full_unstemmed Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer
title_short Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer
title_sort efficacy and prognostic factors for parp inhibitors in patients with ovarian cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308557/
https://www.ncbi.nlm.nih.gov/pubmed/32612955
http://dx.doi.org/10.3389/fonc.2020.00958
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