High risks adverse events associated with trastuzumab emtansine and trastuzumab deruxtecan for the treatment of HER2-positive/mutated malignancies: a pharmacovigilance study based on the FAERS database

作者全名："Ma, Pan; Tian, Hao; Shi, Qiuling; Liu, Ruixiang; Zhang, Yi; Qi, Xiaowei; Chen, Yongchuan"

作者地址："[Ma, Pan; Tian, Hao; Liu, Ruixiang; Zhang, Yi; Qi, Xiaowei; Chen, Yongchuan] First Army Med Univ, Dept Pharm, Chongqing, Peoples R China; [Ma, Pan; Shi, Qiuling] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing, Peoples R China; [Tian, Hao; Zhang, Yi; Qi, Xiaowei] Army Med Univ, Southwest Hosp, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Gaotanyan St 30, Chongqing 40038, Peoples R China; [Chen, Yongchuan] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Dept Pharm, Gaotanyan St 30, Chongqing 400038, Peoples R China"

通信作者："Qi, XW (通讯作者)，Army Med Univ, Southwest Hosp, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Gaotanyan St 30, Chongqing 40038, Peoples R China.; Chen, YC (通讯作者)，Third Mil Med Univ, Army Med Univ, Southwest Hosp, Dept Pharm, Gaotanyan St 30, Chongqing 400038, Peoples R China."

来源：EXPERT OPINION ON DRUG SAFETY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000972128700001

JCR分区：Q3

影响因子：3.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Antibody-drug conjugates; pharmacovigilance analysis; safety signals; adverse events; interstitial lung disease; hepatotoxicity

摘要："BackgroundT-DM1 and T-DXd are two promising antibody-drug conjugates for treating advanced HER2-positive breast cancer and HER2-mutated lung cancer. Understanding the differences in the adverse events (AEs) profile of both drugs may help clinicians make an appropriate treatment decision.Research design and methodsAll data obtained from the FDA Adverse Event Reporting System (FAERS) database from Q1 2004 to Q3 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the AE signals of T-DM1 and T-DXd for comparison.ResultsA total of 2,113 and 1,269 AE reports associated with T-DM1 and T-Dxd, respectively, were retrieved from FAERS database, in which, respondents were mostly elderly women. Their statistical differences (p < 0.001), poses high incidence of thrombocytopenia, including cardiotoxicity (p < 0.05) for T-DM1, while myelosuppression, interstitial lung disease (ILD), and pneumonitis for T-DXd. Splenomegaly, nodular regenerative hyperplasia, hepatic cirrhosis, portal hypertension, neuropathy peripheral, and spider nevus, are particular to T-DM1. Similarly, febrile neutropenia, pneumocystis jirovecii pneumonia, neutrophil count decreased, and KL-6 increased, are unique to T-DXd.ConclusionsT-DXd is more likely to induce ILD/pneumonia and myelosuppression than T-DM1, whereas T-DM1 has higher risk of hepatotoxicity, cardiotoxicity, and thrombocytopenia than T-DXd. T-DM1-related hepatotoxicity may need redefinition. Clinicians may need to balance the benefits and risks of antibody-drug conjugates treatment for certain patients."

基金机构：Chongqing Clinical Pharmacy KeySpecialties Construction Project [CQZDZK003]

基金资助正文：This work was supported by Chongqing Clinical Pharmacy KeySpecialties Construction Project [CQZDZK003].