Reported drug spectrum and disproportionality signals for malignant neoplasm progression in FAERS: a real-world...

Using malignant neoplasm/tumour progression as the endpoint, we screened FAERS for disproportionate reporting signals, characterized the drug spectrum represented in progression-related reports, and prioritized drug-event pairs for further evaluation rather than causal inference.

Publicly available reports from FAERS (2004Q1-2024Q4) and JADER (2004-2024) were analyzed. After FDA-recommended deduplication, malignant tumor progression was identified using the MedDRA Preferred Terms "Malignant neoplasm progression" and "Tumour progression" (version 26.1). Primary and secondary suspect drugs were standardized to generic names using MedEx. Signals were detected by disproportionality analysis using the reporting odds ratio (ROR), with positive signals defined as a report count ≥3 and a lower 95% confidence interval bound >1. The same analytical pipeline was applied to JADER for external validation.

FAERS contained 321,020 progression-related reports; 84,977 unique cases remained after deduplication, rising over time (notably after 2018) with severe outcomes (death 27.63%, hospitalization 13.66%). Among the top 50 drugs, 92% were antineoplastic/immunomodulating agents; nivolumab, pembrolizumab, enzalutamide, everolimus, and osimertinib were most frequently reported. 49 drugs showed positive ROR signals (highest: afatinib, gefitinib, osimertinib); 35/49 were replicated in JADER (8,929 cases).

Progression-related reporting signals were concentrated mainly in immunotherapies and targeted agents. Although disproportionality analysis does not establish causality, these findings may help prioritize drug-event pairs for further investigation and highlight the need for more standardized reporting, as well as confirmatory epidemiologic and mechanistic studies.