KEY TAKEAWAYS
- The study aimed to investigate long-term hepatic adverse reactions of T-DM1 in HER2+ breast cancer.
- Researchers concluded that further research is necessary to optimize T-DM1 treatment duration.
Trastuzumab emtansine (T-DM1) is a widely used second-line (2L) and subsequent therapy for metastatic HER2-positive breast cancer. It has also shown promise in treating early breast cancer, especially in adjuvant settings for patients with residual disease following neoadjuvant chemotherapy. However, there are growing concerns about potential long-term side effects that were not identified during clinical trials.
Hyo Jung Kim and the team aimed to investigate possible safety signals related to T-DM1 in liver and bile duct disorders and to analyze the time it takes for these adverse drug reactions (ADRs) to appear.
They utilized data from the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into 2 groups: those related to T-DM1 (n = 3387) and those related to other drugs (n = 11,833,701).
The results identified a potential safety signal for T-DM1 in liver and bile duct disorders, with a reporting odds ratio (ROR) of 5.66 (95% CI: 5.11-6.27) and an information component (IC) of 2.35 (95% Credibility interval [CrI]: 2.18-2.51).
A subgroup analysis focused on breast cancer cases (2,519 T-DM1; 172,329 other drugs) also showed 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-related liver and bile duct disorders was 41 days. The median times for longer-lasting and chronic disorders were 322.5 days and 301.5 days, respectively.
The study concluded that further research is essential to guide clinical decisions on the optimal duration of T-DM1 treatment, considering the need to balance its therapeutic benefits against the potential risks of liver-related adverse effects.
The study was funded by MSD, Pfizer, AstraZeneca, Novartis, Genome Insight, NGenBio, and Roche.
Source: https://pubmed.ncbi.nlm.nih.gov/39179667
Kim HJ, Yoon JH, Park YH. (2024). “Long-term hepatobiliary disorder associated with trastuzumab emtansine pharmacovigilance study using the FDA Adverse Event Reporting System database.” Sci Rep. 2024;14(1):19587. Published 2024 Aug 23. doi:10.1038/s41598-024-69614-x
