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

Aims

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.

Methods

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.

Results

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 < .05), metastatic renal cell carcinoma (ROR: 220.71, 95% CI: 28.99–1695.41, P < .05) and renal cell carcinoma (ROR: 188.22, 95% CI: 44.24–800.85, P < .05). We also compared the differences in ADRs resulting from different small molecule drug combinations, as well as the differences in ADRs among patients with different types of tumours under combination therapy. Furthermore, we analysed the characteristics of patients prone to experiencing fatal ADRs.

Conclusion

These results can help enhance understanding of the ADRs commonly associated with combination therapy and assist oncologists in formulating screening protocols.