A pharmacovigilance analysis of post-marketing safety of durvalumab

Abstract

Durvalumab has demonstrated significant efficacy in several types of malignancies, while large-scale real-world safety studies remain limited. This study aimed to systematically evaluate the safety of durvalumab through data mining of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We extracted reports of durvalumab as the primary suspected drug from the FAERS database (January 2017 to June 2024). Four disproportionality analysis algorithms were used to detect signals between durvalumab and adverse events (AEs). Durvalumab was recorded in 10,120 reports as the primary suspected drug. Of these, 43.6% of AEs occurred during the first month of treatment, with a median onset time of 40 days (IQR: 14-99 ). Among 181 potential signals, 64 were unexpected preferred terms not listed in the prescribing information, including cytokine release syndrome (CRS), pulmonary tuberculosis, radiation esophagitis, oesophageal fistula, oesophageal perforation, pleural effusion, pneumothorax, cerebral infarction, biliary tract infection, cholecystitis, psoriasiform dermatitis, portal vein thrombosis, acute cholangitis and pericarditis malignant. Serious adverse events accounted for 93.3% of cases. Males exhibited a significantly higher risk of experiencing serious outcomes compared to females (OR = 1.83, 95% CI: 1.52-2.19, P < 0.001). Older age groups demonstrated an elevated risk of severe outcomes relative to those under 65 years (65-74 years: OR = 1.52, 95% CI: 1.15-2.00, P = 0.003; ≥75 years: OR = 1.40, 95% CI: 1.02-1.92, P = 0.038). This study comprehensively assessed the safety of durvalumab and discovered potential new adverse event signals, which may provide critical support for risk identification and monitoring of durvalumab.

Keywords: Adverse events; Cytokine-release syndrome; Durvalumab; FAERS; Pharmacovigilance; Pulmonary tuberculosis.

Fig. 1

Flowchart of identification of positive signals associated with durvalumab from FAERS between Q1 of 2017 and Q2 of 2024.

Fig. 2

Time to onset of AEs with durvalumab as the primary suspected drug.