Single agent and combination checkpoint inhibitors therapy: A post marketing safety analysis.

Abstract

125 Background: Immune Checkpoint Inhibitors (ICIs) are used to treat patients with a wide spectrum of malignancies. Individuals enrolled in clinical trials are usually more fit compared to patients seen in everyday practice. Therefore, it is important to evaluate the safety profile of these agents in real-world data. In addition, it is not clear if the safety of these agents is similar across all age groups. Methods: We reviewed the FDA Adverse Event Reporting System (FAERS) for adverse events associated with the use of PD-1 inhibitors (nivolumab and pembrolizumab); PD-L1 inhibitor (atezolizumab); and CTLA-4 inhibitor (ipilimumab). Our analysis was restricted to reports that included only an ICI as a suspect agent. For each agent, we performed a descriptive analysis of hospitalization (HO) and death (DE) outcomes, as well as select adverse events of special interest (AESI). We compared the distribution of each outcome within age groups ( < 65 years; 67-75; > 75) using Mantel-Haenszel chi -quare test for trend. Results: A total of 23,586 safety reports were included in our analysis. 415 for atezolizumab, 10,026 for nivolumab, 4,808 for pembrolizumab, 6,339 for ipilimumab, and 1,988 for the combination nivolumab plus ipilimumab. Increased age was associated with a statistically significant trend of more hospitalizations for all drugs except for the combination nivolumab plus ipilimumab where hospitalization rate was high ( > 80%) but similar across all age groups. Prevalence of any of the AESI was higher as age increased for all drugs (p < 0.0001) except for atezolizumab (p 0.12) and combination nivolumab plus ipilimumab (p 0.488). Proportion of older patients who experienced death was higher for pembrolizumab (p < 0.001), ipilimumab (p 0.002), and combination nivolumab plus ipilimumab (p < 0.001). Conclusions: Our analysis suggests that among patients treated with ICI, older individuals receiving pembrolizumab, Nivolumab or ipilimumab were more likely to develop immune related AEs, and to be hospitalized. An increased rate of death with higher age was seen with the use of pembrolizumab, ipilimumab, and combination nivolumab + ipilimumab. Older patients treated with ICIs should be monitored carefully for treatment-related AEs.