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.

ABSTRACT

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%, χ2p = 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.