Evaluation of Time to Onset and Outcome of Lung Adverse Events Related to Pembrolizumab Using Marketing Surveillance

Abstract

Background: Pembrolizumab has been widely used in patients since its release, but detailed information on lung-specific adverse events (AEs) from post-marketing monitoring has not been reported. Objectives: This study was undertaken to determine the risk of pembrolizumab-induced lung AEs, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. Method: We analyzed data for the period between April 2004 and March 2022. Data on lung AEs were extracted and the relative risks of AEs were estimated using reporting odds ratios. Results: We analyzed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab, including 3,004 lung AEs. Signals were detected for 14 lung AEs. Interstitial lung disease was the most frequently reported (62.3%) and included fatal cases. A histogram of median time to onset showed occurrence ranging from 2 to 73 days, but some cases of interstitial lung disease occurred after 2 years of administration. The AEs showing the highest fatality rates were interstitial lung disease, respiratory failure, and pneumonia aspiration. Conclusions: This study focused on lung AEs caused by pembrolizumab as post-marketing AEs. Some cases could potentially involve serious outcomes, so patients should be monitored for signs of AE onset not only at the start of administration but also over an extended period, especially for interstitial lung disease.