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

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; I-2 = 48%) and high-grade fatigue (RR, 1.92; 95%CI, 1.51-2.45; p < 0.00001; I-2 = 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.