Efficacy and safety of PARP inhibitors in patients with BRCA-mutated advanced breast cancer: A meta-analysis and systematic review

Ximu Sun; Xin Wang; Jie Zhang; Zhixia Zhao; Xin Feng; Lihong Liu; Zhuo Ma

doi:10.1016/j.breast.2021.08.009

Efficacy and safety of PARP inhibitors in patients with BRCA-mutated advanced breast cancer: A meta-analysis and systematic review

Breast. 2021 Dec:60:26-34. doi: 10.1016/j.breast.2021.08.009. Epub 2021 Aug 21.

Authors

Ximu Sun¹, Xin Wang², Jie Zhang², Zhixia Zhao², Xin Feng³, Lihong Liu⁴, Zhuo Ma⁵

Affiliations

¹ Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No.17, Qi He Lou Street, Dongcheng District, Beijing, 100026, China.
² Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China.
³ Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No.17, Qi He Lou Street, Dongcheng District, Beijing, 100026, China. Electronic address: fengxin1115@ccmu.edu.cn.
⁴ Department of Pharmacy, China-Japan Friendship Hospital, No.2 Yinghuayuan Dongjie, Chaoyang District, Beijing, 100029, China. Electronic address: liulihong@bjcyh.com.
⁵ Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China. Electronic address: mazhuo2013@163.com.

Abstract

Objective: This meta-analysis aimed to investigate the efficacy and safety of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in BRCA-mutated advanced breast cancer patients comprehensively.

Methods: We conducted a systematic literature research through PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, China National Knowledge Infrastructure (CNKI), wanfang, China Biology Medicine disc (CBMdisc), and ClinicalTrials.gov from inception to January 2021. Randomized controlled trials (RCTs) with available data comparing PARP inhibitors versus control therapy in BRCA-mutated advanced breast cancer were eligible for analysis. Statistical analyses were performed with Review Manager (RevMan) version 5.4 and R version 4.0.3.

Results: 1706 studies were retrieved in total, and 4 RCTs with 1540 patients were eligible for meta-analysis finally. The results showed that progression-free survival (PFS) and overall survival (OS) were significantly improved in germline BRCA-mutated breast cancer patients with PARP inhibitors (HR 0.64, 95% CI [0.56-0.74]; HR 0.86, 95% CI [0.74-0.99], respectively) with no significant heterogeneity across studies (I² = 22%, χ² p = 0.28; I² = 0%, χ² p = 0.70, respectively). There was no significant difference in the overall adverse events (AEs), grade≥3 AEs and AEs leading to treatment discontinuation between PARP inhibitor arms and control arms (RR 1.01, 95% CI [0.99-1.02]; RR 0.95, 95% CI [0.83-1.09]; RR 1.17, 95% CI [0.87-1.57], respectively). Based on the available data, PARP inhibitors provided comparable or better results than control arms in improving the quality of life in BRCA-mutated advanced breast cancer patients.

Conclusions: PARP inhibitors prolonged PFS and OS among patients with BRCA-mutated advanced breast cancer with tolerable safety and improved quality of life.

Keywords: BRCA mutation; Breast cancer; Poly(ADP-ribose) polymerase inhibitors; Triple-negative breast cancer.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Antineoplastic Agents* / therapeutic use
Breast Neoplasms* / drug therapy
Breast Neoplasms* / genetics
Female
Humans
Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
Poly(ADP-ribose) Polymerases / therapeutic use
Progression-Free Survival

Substances

Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Poly(ADP-ribose) Polymerases