Differences in Safety Signal Detection Between Osimertinib and First- and Second-Generation EGFR-TKIs: A Pharmacovigilance Study Using a Spontaneous Reporting System.

Aims: This study aimed to evaluate the trends in safety signal detection of osimertinib compared with other epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) through volcano plot analysis, using data from the Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS). The overall objective of this study was to identify the potential risks associated with osimertinib-induced adverse events.

Method: Data were retrieved from the JADER (Q1 2004-Q1 2024) and FAERS (Q4 1997-Q2 2024) databases. The target drugs were osimertinib, gefitinib, erlotinib, and afatinib. Adverse event reports were standardized by converting all records in the database to the preferred terms (PTs) of the International Classification of Diseases and subsequently mapping them to the high-level terms (HLTs) of the Medical Dictionary for Regulatory Activities. Volcano plots of odds ratios and z-scores were generated to assess variations in detection trends between osimertinib and the above-mentioned three EGFR-TKIs. The top 20 HLTs that demonstrated significant safety signals were computed and compared.

Result: The numbers of safety signals detected in the JADER for osimertinib compared to the aforementioned EGFR-TKIs following volcano plot analysis were 24, 20, and 16, whereas detected safety signals were 7, 43, and 14 in FAERS. In the JADER database, the most frequently reported adverse reactions for osimertinib included "poisoning and toxicity" and "heart failure." Conversely, in the FAERS database, the predominant adverse reactions were "death and sudden death" and "marrow depression and hypoplastic anaemias."

Conclusion: This study confirmed an increased frequency of reports linking osimertinib to cardiotoxicity, bone marrow suppression, and anemia. However, interstitial pneumonia, previously considered a risk factor, was not identified. When evaluating risks influenced by racial and treatment-related factors, caution must be exercised regarding potential discrepancies between reported rates and true incidence.