Adverse reactions associated with nivolumab and small molecule antiangiogenic drugs: A pharmacovigilance analysis

Immune checkpoint inhibitors, such as nivolumab, combined with small molecule antiangiogenic receptor tyrosine kinase inhibitors (TKIs), present a promising strategy for future immunotherapy. However, combination therapy can lead to specific adverse drug reactions (ADRs) in various clinical settings. Current research on the ADRs associated with combination therapy is limited. Our study aims to assess the safety of combination therapy. We extracted ADR reports on combination therapy from the Food and Drug Administration (FDA) Adverse Event Reporting System database, covering the period from the first quarter of 2012 to the third quarter of 2023, and conducted a large-scale retrospective study. We evaluated ADR risk signals using the reporting odds ratio (ROR) and calculated the Ro/e ratio to compare the differences in the risk of fatal ADRs among various tumour types. We comprehensively reported the occurrence of ADRs in pan-cancer patients undergoing combination therapy. The combination therapy significantly increased the risk of sensitive skin (ROR: 231.43, 95% CI: 55.01-973.72, P