Evaluation of Times-to-onset and Outcomes of Lung Adverse Events Associated With Sorafenib Using JADER.

Abstract

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

Patients and methods: Data for the period between April 2004 and May 2023 were analyzed. Data on lung AEs were extracted, and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs).

Results: A total of 2,230,863 reports were analyzed, and 8,374 reports of AEs associated with sorafenib, including 381 lung AEs, were identified. Signals were detected for two lung AEs: metastases to the lung and tracheal hemorrhage. Fatal outcomes were observed for both AEs. Histograms of the median times to onset of the two detected lung AE signals showed that AEs occurred from 49 to 275 days after sorafenib administration. Weibull distributions showed that the incidences of these AEs occurred constantly throughout the exposure period (random failure type).

Conclusion: This study focused on lung AEs associated with sorafenib, highlighting serious outcomes such as lung metastases and tracheal hemorrhage. Continuous monitoring for these AEs is crucial from treatment initiation through the entire therapy course.