Evaluation of Lung Adverse Events Associated With Lenvatinib: A Post-marketing Surveillance Study

Abstract

Background/aim: Despite the seriousness of lung adverse events (AEs) associated with lenvatinib, comprehensive data on these events remain limited. This study was conducted to examine the disproportionality, time to onset, incidence rates, and outcomes of lenvatinib-associated lung AEs using the Japanese Adverse Drug Event Report database.

Patients and methods: We analysed data for the period from April 2004 to May 2023. Data on lung AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Weibull distribution parameters were also calculated.

Results: Among the 2,230,863 reports analysed, 7,684 reports of AEs associated with lenvatinib were identified, including 380 lung AEs. Signals were detected for three lung AEs: tracheal fistula, tracheo-oesophageal fistula, and tracheal haemorrhage. Fatal outcomes were observed for tracheal fistula and tracheal haemorrhage. A histogram of median times to onset indicated that lung AEs associated with lenvatinib occurred 15-111 days after administration. Weibull distributions showed that the incidence of these AEs remained constant throughout the exposure period (random failure type).

Conclusion: The present study highlights post-marketing AEs associated with lenvatinib, with a particular focus on lung AEs. Tracheal fistula and tracheal haemorrhage were identified as AEs with potentially serious outcomes following lenvatinib administration. Monitoring patients for early signs of these AEs is important not only at treatment initiation, but also throughout the entire course of therapy.

Keywords: Japanese Adverse Drug Reaction Reporting database; Lenvatinib; lung adverse event; outcome; time to onset.