Risk of fatigue with PARP inhibitors in cancer patients: a systematic review and meta-analysis of 29 phase II/III randomized controlled trials

Abstract

Fatigue was a frequently reported adverse event associated with the use of PARP inhibitors. We performed a systematic review and meta-analysis to fully investigate the fatigue of PARP inhibitors in cancer patients. Databases were searched for randomized controlled trials (RCTs) treated with PARP inhibitors till July 2020. Twenty-nine RCTs and 9479 patients were included. This meta-analysis suggests that the use of PARP inhibitors significantly increase the risk of developing all-grade (RR, 1.25; 95%CI, 1.20–1.31; p < 0.00001; I² = 48%) and high-grade fatigue (RR, 1.92; 95%CI, 1.51–2.45; p < 0.00001; I² = 11%). Veliparib was associated with a relatively lower risk of fatigue. Patients with ovarian cancer tend to be associated with a higher risk of fatigue than those with non-ovarian cancer. Longer duration of therapy was associated with a higher risk of all-grade fatigue. Patients receiving PARP inhibitor monotherapy tends to be associated with a higher risk of all-grade fatigue than those receiving combination treatment.

Keywords:

• PARP inhibitors
• Cancer
• Fatigue
• Meta-analysis
• Systematic review
• RCTs

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Conflict of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work is supported by National Key Research and Development Program of China (2019YFC1712503), Basic Research Programs of Science and Technology Department of Sichuan Province (2020JY0277) and Fundamental Research Funds for the Central Universities, Southwest Minzu University (2021HQZZ03).

Notes on contributors

Jing Li

Jing LI, MS., is currently an associate professor of College of Pharmacy of Southwest Minzu University. She specializes in medical statistics, pharmacokinetic, and clinical pharmacy.

Zhifeng Zhang

Zhifeng ZHANG, PhD., is currently a professor of College of Pharmacy of Southwest Minzu University. He specializes in medical statistics, pharmacokinetic, and pharmacodynamics.