PARP inhibitors linked to increased risk of pneumonitis

Jason M. Broderick

Treatment with PARP inhibitors is associated with an increased risk of pneumonitis, according to recently a recent published paper.1

The PARP inhibitors olaparib (Lynparza) and rucaparib (Rubraca) are recent additions to the prostate cancer armamentarium, and adverse event (AE) management is critical to their optimal integration into clinical practice.

“PARP inhibitors 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,” the investigators wrote.

The paper comprised 2 components, a meta-analysis of randomized controlled trials (RCTs) and a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database. The meta-analysis consisted of a review of RCTs with available results reporting incidents of pneumonitis in patients treated with PARP inhibitors.

RCTs with available data reporting pneumonitis events with PARP inhibitors were eligible for the meta-analysis. These PARP inhibitor RCTs could be for patients with various tumor types, such as prostate, ovarian, breast, and pancreatic. The FAERS database was intended to characterize the primary characteristics of pneumonitis related to treatment with PARP inhibitors.

Overall, the metanalysis included 5771 patients across 16 trials. Pneumonitis was reported in 0.79% of patients treated with PARP inhibitors compared with 0.24% of patients across the various control arms. Although these overall incident rates were not high, the risk of pneumonitis was significantly higher in patients receiving PARP inhibitors (odd ratio, 2.68; P = .007).

The real-world data review of the FAERS database found 84 patients with pneumonitis related to PARP inhibitor treatment. Follow-up was possible for 79 of these patients, 16% of whom had died of pneumonitis. The median time to the development of pneumonitis was 81 days (interquartile range, 27-131 days), and 87% of patients experienced the onset of pneumonitis within 6 months.

In the prostate cancer armamentarium, olaparib and rucaparib are both specifically approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

PARP inhibitor–related AEs in patients with mCRPC were a recent topic of discussion in Urology Times’s case review video series, Around the Practice. Watch the video for additional insight on this increasingly important topic in urology.

Reference

1. Ma Z, Sun X, Zhao Z, et al. 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 [published online ahead of print May 19, 2021]. Gynecol Oncol. doi: 10.1016/j.ygyno.2021.05.012