Reported Drug Spectrum and Disproportionality Signals for Malignant Neoplasm Progression in FAERS: A Real-World Pharmacovigilance Study

Abstract

This study aimed to identify drugs disproportionately reported with malignant neoplasm progression, an uncommon but clinically important endpoint, using large spontaneous reporting systems. Public reports were analyzed from the FDA Adverse Event Reporting System (FAERS; 2004Q1-2024Q4) and the Japanese Adverse Drug Event Report database (JADER; 2004-2024). Cases were defined using MedDRA Preferred Terms for malignant neoplasm/tumour progression, and reports in which progression was recorded as an indication or medical history were excluded. Suspected drugs were standardized to generic names, and disproportional reporting was quantified using reporting odds ratios (RORs). Signals identified in FAERS were examined in JADER for cross-validation.FAERS contained 321,020 progression-related reports, corresponding to 84,977 unique cases after deduplication. Reporting increased over time and was associated with severe outcomes (death 27.63%; hospitalization 13.66%). Among the 50 drugs prioritized by report volume and signal strength, most were anticancer or immunomodulating agents (64%), and the highest report counts involved pembrolizumab, nivolumab, carboplatin, and enzalutamide. Disproportionality analysis detected positive signals for 41 drugs, with the strongest signals observed for afatinib, gefitinib, and osimertinib. In JADER (8,929 cases), 22 of the 41 FAERS-positive signals were replicated with consistent direction but different magnitude.These findings are hypothesis-generating and suggest that tumor progression reporting clusters around specific therapies, particularly immunotherapies and targeted agents.These results support closer post marketing monitoring of selected drug event pairs and incentivize epidemiological and case-control studies to validate signals and elucidate clinical significance.

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