Haemorrhage-related adverse events profles of lenvatinib and pembrolizumab alone or in combination: a real-world pharmacovigilance study based on FAERS database.

Abstract

Objective: Limited understanding exists regarding the haemorrhagic risk resulting from potential interactions between lenvatinib and pembrolizumab. We investigated haemorrhagic adverse events (ADEs) associated with co-administration of lenvatinib and pembrolizumab using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) in an effort to provide recommendations for their safe and sensible use.

Methods: The FAERS database's bleeding events linked to lenvatinib and pembrolizumab were carefully examined. Haemorrhagic signals mining was performed by the reported odds ratios (RORs) and information component (IC), corroborated by additive and multiplicative models.

Results: A total of 38,416,055 adverse event cases were analyzed, with 1188 bleeding events records in the lenvatinib alone, 952 bleeding events records in the pembrolizumab alone and 420 bleeding events reports in the combination therapy, respectively. We observed a significantly higher risk of haemorrhage with the combination of lenvatinib and pembrolizumab compare with pembrolizumab alone. In addition, in the baseline model analysis of suspected bleeding adverse reactions, the additive model detected an increased incidence of small intestinal haemorrhage caused by combination therapy, and found no risk signals of tumour haemorrhage and tracheal haemorrhage; the results of multiplicative model are all negative.

Conclusion: The analysis of FAERS data reveals different levels of haemorrhagic risk when lenvatinib and pembrolizumab are administered concurrently, highlighting the significance of being cautious when using them in clinical practice.