Analysis Of Adverse Reactions Of Carbotinib Combined With Immunotherapy(Database Of FAERS)

Background:Cabozantinib is a multi-target,targeted drug with anti-angiogenesis properties.FDA approved indications include medullary thyroid cancer,kidney cancer and liver cancer.In recent years,clinical trials have explored the efficacy of cabotinib combined with immunotherapy in kidney and liver cancer.Clinical trial results show that cabotinib combined with immunotherapy is effective,but with increased toxicity.Doctors need to be alert to side effects in clinical use of drugs.In this study,FAERS database was used to explore and analyze the adverse reactions of cabotinib combined with immunotherapy.Purpose of research:1.Baseline characteristics and tumor species distribution of patients treated with cabotinib combined with immunotherapy were analyzed;2.Report odds ratio(ROR)of Preferredterms(PT)for adverse reactions of different drug combinations was calculated to find meaningful signals of adverse reactions;3.Univariate and multivariate logistic regression analysis was conducted for adverse reactions of different drug combinations and SOC,to explore the relationship between different drug combinations and SOC;4.Multiple logistic regression analysis was carried out by tumor species to explore the risk or protective factors among different tumor species;5.Multiple logistic regression analysis was performed by tumor species to explore the risk or protection factors in different tumor species.Method:Data from the FAERS pharmacovigilance database were retrieved from all adverse events reported with Cabozantinib during the year of initial FDA approval through March 31,2020(last accessed:August 2,2022).To ensure a uniform standard for statistical analysis,the names of the reports collected were coded according to PT of the MedialDictionaryForreg-ulatoryaetivitie(MedDRA).The collected reports were statistically classified according to MedDRA’s organ/system grading criteria in order to accurately count the organs/systems affected by ADR.The association between different drug combinations and adverse reactions was determined by the reporting Odds ratio(ROR)algorithm based on disproportionality analysis.R statistical software V.3.5.1 was used for data processing,statistical analysis and plotting.Result:In this study,we found that most of the adverse reactions related to single drug cabotinib were cutaneous mucosal reactions,and no hemorrhagic adverse reactions of moderate intensity were found.Moderate intensity immunomediated adverse reactions were found in carbotinib combined with navulizumab,carbotinib combined with navulizumab,ipilimumab,and navulizumab combined with attilizumab,such as immune hepatitis,immune nephritis,and immune enteritis.Different drug combinations have different effects on adverse reactions of various systems in different tumor species.Cabotinib combined with ipilimumab and cabotinib combined with navuliumab are protective factors for adverse drug reactions of renal and urinary systems in kidney and liver cancer.Cabotinib combined with PD-L1 was a risk factor for drug-related cardiac impairment in kidney and liver cancer,but was not significant in prostate,bladder and lung cancer.Among different tumor species,different age stages have different effects on the adverse reactions of various systems.In prostate cancer,young people are more likely to have drug-related adverse reactions of endocrine system than the elderly.Conclusion:In this study,we found moderate intensity associated immune-mediated adverse reactions in carbottinib combined with navulizumab,carbottinib combined with navulizumab,ipilimumab,and navulizumab combined with attilizumab.Compared with cabotinib alone,combination therapy may cause more adverse effects,but it may also be a protective factor for systemic adverse reactions in different cancers.Different age and sex may correspond to different systemic adverse reactions,and there are differences in different tumor species.