Evaluation of lung adverse events with trastuzumab using the Japanese pharmacovigilance database

Abstract The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analysed 1,772,494 reports and identified 4,362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary oedema, pleural effusion, lung disorder, acute pulmonary oedema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105 days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease.