Risk of pneumonitis in cancer patients treated with PARP inhibitors: A meta-analysis of randomized controlled trials and a pharmacovigilance study of the FAERS database

Objective/Background. We aimed to evaluate the risk of PARP inhibitors (PARPis) causing pneumonitis in randomized controlled trials (RCTs) and in the real-world practice. Methods. First, a systematic review based on meta-analysis was conducted. RCTs with available data reporting pneumonitis events for PARPis were eligible for analysis. Second, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the main features of PARPi-related pneumonitis. Results. 16 trials with 5771 patients were included in our meta-analysis. Compared with control arms, PARPis showed a significant increase in the risk of pneumonitis events (Peto OR 2.68 [95% CI 1.31-5.47], p = 0.007) with no heterogeneity (I2 = 0%, chi 2 p = 0.70). The incidence of pneumonitis across treatment arms was 0.79% (28/ 3551). In the FAERS database, we identified 84 cases of PARPi-pneumonitis with a fatality rate of 16% (13/79). The median time to event onset was 81 (interquartile range [IQR] 27-131) days and 87% of the adverse events occurred within 6 months. Conclusion. PARPis increased the risk of pneumonitis that can result in serious outcomes and tend to occur early. Early recognition and management of PARPi-pneumonitis is of vital importance in clinical practice. The mechanisms and risk factors should be studied further to improve clinical understanding and innovative treatment strategies for these diseases. (c) 2021 Published by Elsevier Inc.

Automated summary

PARP inhibitors increase the risk of pneumonitis in clinical practice, which can lead to serious outcomes and tend to occur early. Early recognition and management of PARPi-pneumonitis is crucial.