Risk comparison of adverse reactions among gemcitabine monotherapy, gemcitabine combined with cisplatin, gemcitabine combined with PD-1/PD-L1 inhibitors treatment: insights from the FDA adverse event reporting system database

Background Although gemcitabine (GEM) has long been the standard treatment for cancer, its combination with other drugs has shown better therapeutic effects. Therefore, our study sought to evaluate and compare the risk of adverse events (AEs) with GEM, GEM combined with cisplatin, GEM combined with PD-1 inhibitors (pembrolizumab and nivolumab), and GEM combined with the PD-L1 inhibitor (durvalumab) treatment. Method Based on the data extracted from the FAERS database from Q1 2004 to Q4 2024, including GEM as the primary suspected (PS) drug and GEM as PS plus cisplatin/pembrolizumab/nivolumab/durvalumab as a secondary suspect (SS), concomitant drug (C), or interacting drug (I), the risk of AEs was investigated through reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Furthermore, time-to-onset (TTO) analysis was carried out to further understand the pattern of AE occurrence. Results Between Q1 2004 and Q4 2024, a total of 20,135 GEM-related, 3,647 GEM combined with cisplatin-related, 152 GEM combined with pembrolizumab-related, 107 GEM combined with nivolumab-related, and 391 GEM combined with durvalumab-related AEs were collected. At the system organ categories (SOC) level, blood and lymphatic system disorders was the common positive SOC for five treatment groups. At the preferred terms (PT) level, there were three common AEs among five treatment groups, namely thrombocytopenia, neoplasm progression, and pneumonitis. Among the three AEs, the risk of thrombocytopenia was the highest in the GEMcombined with cisplatin treatment group [ROR(95%CI) = 18.12 (16.22-20.23)], and the risk of neoplasm progression and pneumonitis was the highest in the GEMcombined with durvalumab [neoplasm progression: ROR(95%CI) = 28.19 (16.62-47.83); pneumonitis: ROR(95%CI) = 31.41 (17.32-56.95)]. Notably, most AEs among five treatment groups occurred within 30 days. Conclusion These findings highlight the safety profiles of GEM, as well as GEM combination therapy, and offer important insights to enhance the clinical use and minimize potential adverse effects.