Abstract
PD-1/PD-L1 inhibitors provide new opportunities to reduce global burden of lung cancer. However, adverse drug events (ADEs) pose significant risks to patient health, warranting systematic attention. Data on ADEs associated with PD-1/PD-L1 inhibitors for lung cancer treatment were collected from FDA Adverse Event Reporting System (FAERS) database between January 2014 and June 2023. Logistic regression was used to explore potential factors related to death. Signal mining for ADEs was performed using reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods, which revealed toxicity characteristics of these inhibitors among different system organ classes (SOCs) in terms of the number of both ADEs and ADE signals, and the signal strength. Additionally, factors associated with the timing of the first ADE were analyzed using Mann-Whitney U or Kruskal-Wallis tests. A total of 36,387 reports were collected. It is indicated that patients aged 65 years above, male, with small-cell lung cancer, treated with PD-1 inhibitors, without chemotherapy combination, experiencing earlier first ADE occurrence, and with more ADEs were at higher risk of death. Signal mining revealed 175, 189, 74, and 123 ADE signals for nivolumab (N), pembrolizumab (P), durvalumab (D), and atezolizumab (A), respectively. For SOC characteristics, ADEs associated with N were most frequently distributed in 'General disorders and administration site conditions', with the highest signal strength in 'Endocrine disorders'. P had the highest ADE signal frequency and strength in 'Immune system disorders'. For D, the highest frequency of ADEs and ADE signals, and the highest signal strength were in 'Respiratory, thoracic, and mediastinal disorders'. Uniquely, A exhibited significant signal strength in 'Blood and lymphatic system disorders'. 'Blood and lymphatic system disorders' and 'Endocrine disorders' had the earliest and latest ADE onset respectively. Death outcome and chemotherapy combinations were associated with earlier onset. And significant timing differences existed among different inhibitors. Based on 36,387 reports, this study comprehensively reveals the characteristics of ADEs associated with PD-1/PD-L1 inhibitors, providing valuable reference for their future clinical practice.