Interstitial lung disease in patients treated with poly (ADP-ribose) polymerase inhibitors (PARPi): analysis of results from clinical trials and the FDA Adverse Events Reporting System database.

OBJECTIVE: To evaluate the risk of interstitial lung disease associated with poly (ADP-ribose) polymerase inhibitors (PARPi) and characterize its clinical features. METHODS: We systematically reviewed phase III randomized clinical trials of interstitial lung disease related to PARPi and calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs). Pharmacovigilance studies were conducted by collecting cases of PARPi-related interstitial lung disease from the FDA Adverse Events Reporting System and assessing disproportionalities by reporting ORs and information components. RESULTS: A total of five randomized clinical trials involving 2980 patients were included. Although PARPi showed a tendency to increase the risk of interstitial lung disease compared with controls, this difference was not significant (Peto OR: 4.92; 95% CI: 0.92 to 26.35). A total of 170 cases of interstitial lung disease related to PARPi were included, with a median latency of 99 days. PARPi had a significantly increased reporting of interstitial lung disease (reporting OR: 2.86; 95% CI: 2.46 to 3.33; information component (IC): 1.49; 95% CI: 1.28 to 1.74). Our sensitivity analyses showed strong robustness of the disproportionalities between PARPi as a class, olaparib, and interstitial lung disease. Some 91.9% of patients experienced discontinuation, 51.6% achieved remission, and no deaths were reported. CONCLUSION: Our pharmacovigilance study suggested increased reporting of interstitial lung disease related to PARPi particularly olaparib.