Gastrointestinal events with PARP inhibitors in cancer patients: A meta-analysis of phase II/III randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE

PARP inhibitors are currently one of the most promising PARP targeted drugs for patients with certain types of cancer. Gastrointestinal (GI) events are common adverse events for all PARP inhibitors. We conducted this meta-analysis of randomized controlled trials (RCTs) to fully investigate the incidence and the relative risk of GI events in cancer patients receiving PARP inhibitors.

STUDY DESIGN

Randomized controlled trials in cancer patients treated with PARP inhibitors were retrieved, and the systematic evaluation was conducted. Embase and PubMed/Medline were searched for articles published till July 2020.

RESULTS

Twenty-nine RCTs and 9529 patients were included. The present meta-analysis suggests that the use of PARP inhibitors significantly increases the risk of developing all-grade nausea (RR, 1.46; 95% CI, 1.29-1.66; p < .00001), vomiting (RR, 1.39; 95% CI, 1.17-1.64; p = .0001), diarrhoea (RR, 1.14; 95% CI, 1.06-1.23; p = .0003) and decreased appetite (RR, 1.24; 95% CI, 1.14-1.36; p < .00001), but not for constipation. And the use of these agents significantly increased the risk of high-grade nausea (RR, 1.99; 95% CI, 1.44-2.74; p < .0001), vomiting (RR, 1.54; 95% CI, 1.11-2.14; p = .01) and decreased appetite (RR, 2.03; 95% CI, 1.22-3.40; p = .007), except for diarrhoea and constipation. Nausea was the most common GI event for these agents. Patients receiving veliparib were associated with a relatively lower risk of all-grade nausea and vomiting. Patients with ovarian cancer tend to have a higher risk of all-grade nausea and vomiting than those with non-ovarian cancer. The risk of all-grade nausea and vomiting tended to be higher when PARP inhibitors treatment was longer.

WHAT IS NEW AND CONCLUSION

PARP inhibitors were associated with a significant increased risk of GI events. Clinicians should be aware of these risks and perform regular monitoring.