未经批准:曲妥珠单抗可改善HER2过表达恶性肿瘤患者的预后,但与左心室射血分数降低相关。其他抗HER2疗法的心力衰竭(HF)风险尚不清楚。
UNASSIGNED:使用世界卫生组织的药物警戒数据,作者比较了不同抗HER2方案的HF几率.
未经评估:在VigiBase中,41,976例患者使用抗HER2单克隆抗体(曲妥珠单抗,n=16,900;帕妥珠单抗,n=1,856),抗体-药物缀合物(曲妥珠单抗emtansine[T-DM1],n=3,983;曲妥珠单抗地克替康,n=947),和酪氨酸激酶抑制剂(阿法替尼,n=10,424;拉帕替尼,n=5,704;neratinib,n=1,507;图卡替尼,n=655);此外,36,052例患者使用以抗HER2为基础的联合治疗方案出现ADR。大多数患者患有乳腺癌(单一疗法,n=17,281;组合,n=24,095)。结果包括相对于曲妥珠单抗,每种单一疗法的HF几率比较,在每个治疗类别中,在组合方案中。
未经批准:16,900名曲妥珠单抗相关不良反应患者,2,034(12.04%)有HF报告(中位发病时间5.67个月;IQR:2.85-9.32个月),而抗体-药物缀合物则为1%至2%。在总体队列(报告OR[ROR]:17.37;99%CI:14.30-21.10)和乳腺癌亚组(ROR:17.10;99%CI:13.12-22.27)中,曲妥珠单抗相对于其他抗HER2治疗有更高的HF报告几率。帕妥珠单抗/T-DM1的HF报告几率是T-DM1单药治疗的3.4倍;图卡替尼/曲妥珠单抗/卡培他滨的几率与图卡替尼相似。在转移性乳腺癌治疗方案中,曲妥珠单抗/帕妥珠单抗/多西他赛的HF几率最高(ROR:1.42;99%CI:1.17-1.72),拉帕替尼/卡培他滨的HF几率最低(ROR:0.09;99%CI:0.04-0.23)。
未经批准:曲妥珠单抗和帕妥珠单抗/T-DM1比其他抗HER2疗法具有更高的HF报告几率。这些数据提供了大规模,关于哪些HER2靶向方案将受益于左心室射血分数监测的真实世界洞察.
UNASSIGNED: Trastuzumab improves outcomes in patients with HER2-overexpressing malignancies but is associated with decreases in left ventricular ejection fraction. Heart failure (HF) risks from other anti-HER2 therapies are less clear.
UNASSIGNED: Using World Health Organization pharmacovigilance data, the authors compared HF odds across anti-HER2 regimens.
UNASSIGNED: In VigiBase, 41,976 patients had adverse drug reactions (ADRs) with anti-HER2 monoclonal antibodies (trastuzumab, n = 16,900; pertuzumab, n = 1,856), antibody-drug conjugates (trastuzumab emtansine [T-DM1], n = 3,983; trastuzumab deruxtecan, n = 947), and tyrosine kinase inhibitors (afatinib, n = 10,424; lapatinib, n = 5,704; neratinib, n = 1,507; tucatinib, n = 655); additionally, 36,052 patients had ADRs with anti-HER2-based combination regimens. Most patients had breast cancer (monotherapies, n = 17,281; combinations, n = 24,095). Outcomes included comparison of HF odds with each monotherapy relative to trastuzumab, within each therapeutic class, and among combination regimens.
UNASSIGNED: Of 16,900 patients with trastuzumab-associated ADRs, 2,034 (12.04%) had HF reports (median time to onset 5.67 months; IQR: 2.85-9.32 months) compared with 1% to 2% with antibody-drug conjugates. Trastuzumab had higher odds of HF reporting relative to other anti-HER2 therapies collectively in the overall cohort (reporting OR [ROR]: 17.37; 99% CI: 14.30-21.10) and breast cancer subgroup (ROR: 17.10; 99% CI: 13.12-22.27). Pertuzumab/T-DM1 had 3.4 times higher odds of HF reporting than T-DM1 monotherapy; tucatinib/trastuzumab/capecitabine had similar odds as tucatinib. Among metastatic breast cancer regimens, HF odds were highest with trastuzumab/pertuzumab/docetaxel (ROR: 1.42; 99% CI: 1.17-1.72) and lowest with lapatinib/capecitabine (ROR: 0.09; 99% CI: 0.04-0.23).
UNASSIGNED: Trastuzumab and pertuzumab/T-DM1 had higher odds of HF reporting than other anti-HER2 therapies. These data provide large-scale, real-world insight into which HER2-targeted regimens would benefit from left ventricular ejection fraction monitoring.