Safety profile of poly (ADP-ribose) polymerase (PARP) inhibitors in cancer: a network meta-analysis of randomized controlled trials.

Content Provider	Europe PMC
Author	Bao, Shengnan Yue, Yuanping Hua, Yijia Zeng, Tianyu Yang, Yiqi Yang, Fan Yan, Xueqi Sun, Chunxiao Yang, Mengzhu Fu, Ziyi Huang, Xiang Li, Jun Wu, Hao Li, Wei Zhao, Yang Yin, Yongmei
Copyright Year	2021
Abstract	BackgroundPoly (ADP-ribose) polymerase (PARP) inhibitors, which are among the most important breakthroughs in precision medicine, have played a crucial role in cancer treatment. Understanding the toxicity profiles of the different PARP inhibitors will improve strategic treatment in clinical practice.MethodsPubMed, Cochrane Library, and Web of Science were systematically searched to include related studies published in English between January 2009 and February 2020. Only prospective, phase II and III randomized controlled trials were included. The following treatment groups were analyzed: niraparib, talazoparib, olaparib, rucaparib, conventional therapy (chemotherapy), one PARP inhibitor with one angiogenesis inhibitor, and placebo. Baseline data and adverse event data were extracted from the Bayesian random-effects network meta-analysis.ResultsFourteen phase II and III randomized controlled trials (4,336 patients) were included. When considering grade 3–5 adverse events, olaparib may be a better choice (probability =57%), followed by conventional therapy (50%), talazoparib (45%), rucaparib (75%), niraparib (77%), and a PARP inhibitor with one angiogenesis inhibitor (94%). Niraparib and rucaparib had higher risks for hematological and gastrointestinal toxicities, respectively. Talazoparib was safer for gastrointestinal function. Constipation and neutropenia were less observed in olaparib, but the risks for anorexia increased. The combination of PARP inhibitor and angiogenesis inhibitor increased the risk of general, metabolic, and gastrointestinal disorders.ConclusionsThis network meta-analysis suggested that the toxicity spectrum of each PARP inhibitor is different. Olaparib had the best safety profile among all PARP inhibitors because of its mild toxicity and narrow spectrum. This study may guide clinicians and support further research.
ISSN	23055839
Volume Number	9
PubMed Central reference number	PMC8421942
Issue Number	15
PubMed reference number	34532366
Journal	Annals of Translational Medicine [Ann Transl Med]
e-ISSN	23055847
DOI	10.21037/atm-21-1883
Language	English
Publisher	AME Publishing Company
Publisher Date	2021-08-01
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0. 2021 Annals of Translational Medicine. All rights reserved.
Subject Keyword	Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) network meta-analysis adverse events randomized controlled trials
Content Type	Text
Resource Type	Article
Subject	Medicine