A Disproportionality Analysis of Immune Checkpoint Inhibitors in Combination With Platinum-Based Agents Using the FDA Adverse Event Reporting System Database

Abstract

Objective: Immune checkpoint inhibitors (ICIs) combined with platinum-based compounds are commonly used in the treatment of certain malignant tumors. This study aims to analyze adverse events (AEs) associated with the combination therapy of ICIs and platinum-based compounds by using the FAERS database.

Methods: This study retrieved relevant adverse event (AE) data from the FAERS database (2008-2024) and conducted a retrospective analysis of the collected AEs. Multiple disproportionality analysis algorithms were employed, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

Results: Analysis of 28,585 reports identified 27 significant SOC-level signals, strongest for hematological (ROR = 6.3), endocrine (ROR = 14.3), and hepatobiliary disorders (ROR = 4.49). Key PTs included malignant neoplasm progression (ROR = 16), febrile neutropenia (ROR = 15.31), and myocarditis (ROR = 16.3). 45.5% of AEs occurred within 1 month (median onset: 38 days). Combination therapy showed lower rates vs. monotherapy for malignancy progression and nephrotoxicity, but higher neurotoxicity (628 neuropathy cases).

Conclusion: The combination exhibits distinct early-onset toxicities (early-onset hematological/endocrine/hepatic) and novel risks (neuropathy/myocarditis/leukemia), necessitating enhanced initial monitoring and subgroup-specific management.

Keywords: FAERS; disproportionality analysis; immune checkpoint inhibitors; platinum‐based agents.