Long-term hepatobiliary disorder associated with trastuzumab emtansine pharmacovigilance study using the FDA Adverse Event Reporting System database.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Ado-Trastuzumab Emtansine*/adverse effects ; Ado-Trastuzumab Emtansine*/therapeutic use ; Adverse Drug Reaction Reporting Systems* ; United States Food and Drug Administration* ; Pharmacovigilance* ; Breast Neoplasms*/drug therapy; Humans ; United States ; Female ; Middle Aged ; Databases, Factual ; Chemical and Drug Induced Liver Injury/etiology ; Chemical and Drug Induced Liver Injury/epidemiology ; Trastuzumab/adverse effects ; Adult ; Antineoplastic Agents, Immunological/adverse effects ; Aged ; Biliary Tract Diseases/chemically induced ; Liver Diseases/epidemiology

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11-6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18-2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92-3.68; IC = 1.53, 95%CrI = 1.35-1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.
(© 2024. The Author(s).)

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2021R1I1A1A01058250 National Research Foundation of Korea(NRF), funded by the Ministry of Education; RS-2023-00241523 National Research Foundation of Korea(NRF), funded by the Ministry of Education; SMO122003 Samsung Medical Center

Keywords: FDA Adverse Event Reporting System; Hepatobiliary disorder; Pharmacovigilance; Post-marketing surveillance; Real-world data; Trastuzumab emtansine

SE2KH7T06F (Ado-Trastuzumab Emtansine)
P188ANX8CK (Trastuzumab)
0 (Antineoplastic Agents, Immunological)

Date Created: 20240823 Date Completed: 20240823 Latest Revision: 20240826

20240826

PMC11343769

10.1038/s41598-024-69614-x

39179667