Perez Edith A, Koehler Maria, Byrne Julie, Preston Alaknanda J, Rappold Erica, Ewer Michael S
Division of Hematology/Oncology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA.
Mayo Clin Proc. 2008 Jun;83(6):679-86. doi: 10.4065/83.6.679.
To analyze the cardiac safety of lapatinib, an oral, reversible, tyrosine kinase EGFR (ERBB1) and HER2 inhibitor, using prospective data collected in 44 clinical studies.
Lapatinib (as monotherapy or in combination) was administered to 3689 patients in studies conducted between January 5, 2001, and September 30, 2006. Left ventricular ejection fraction (LVEF) was prospectively evaluated via multiple-gated acquisition scan or echocardiography at screening, every 8 weeks during therapy, and at withdrawal. We analyzed cardiac events defined as symptomatic (grade 3 or 4 left ventricular systolic dysfunction according to the National Cancer Institute Common Terminology Criteria for Adverse Events) or asymptomatic (LVEF decreases > or = 20% relative to baseline and below the institution's lower limit of normal; no symptoms).
A study-defined cardiac event was reported in 60 patients (1.6%) previously treated with anthracyclines (n=12), trastuzumab (n=14), or neither (n=34). These prior treatments were associated with a 2.2%, 1.7%, and 1.5% incidence of cardiac events, respectively. In most patients (53 patients, 83%), events were not preceded by symptoms. Mean times to onset and duration of LVEF decrease were 13.0 and 7.3 weeks, respectively. The decrease in LVEF was rarely severe; the mean nadir was 43%. In 40 patients for whom outcome was determined, 35 (88%) had a partial or full recovery regardless of continuation or discontinuation of lapatinib. No cardiac deaths occurred among patients treated with lapatinib.
Our review of data from 44 clinical studies revealed low levels of cardiotoxicity for lapatinib. Cardiac events were usually asymptomatic, caused reversible decreases in LVEF, and occurred at similar rates in patients who were and were not pretreated with anthracyclines or trastuzumab.
利用44项临床研究收集的前瞻性数据，分析口服、可逆性酪氨酸激酶表皮生长因子受体（ERBB1）及人表皮生长因子受体2（HER2）抑制剂拉帕替尼的心脏安全性。
在2001年1月5日至2006年9月30日开展的研究中，3689例患者接受了拉帕替尼治疗（单药治疗或联合治疗）。在筛选时、治疗期间每8周以及停药时，通过多门控采集扫描或超声心动图前瞻性评估左心室射血分数（LVEF）。我们分析了定义为有症状的心脏事件（根据美国国立癌症研究所不良事件通用术语标准为3级或4级左心室收缩功能障碍）或无症状的心脏事件（LVEF相对于基线下降≥20%且低于机构正常下限；无症状）。
60例患者（1.6%）报告了研究定义的心脏事件，这些患者既往接受过蒽环类药物治疗（n = 12）、曲妥珠单抗治疗（n = 14）或均未接受过上述治疗（n = 34）。这些既往治疗分别与2.2%、1.7%和1.5%的心脏事件发生率相关。在大多数患者（53例，83%）中，事件发生前并无症状。LVEF下降的平均起始时间和持续时间分别为13.0周和7.3周。LVEF下降很少严重；平均最低点为43%。在结局已确定的40例患者中，35例（88%）部分或完全恢复，无论是否继续使用拉帕替尼。接受拉帕替尼治疗的患者中未发生心脏死亡。
我们对44项临床研究数据的回顾显示，拉帕替尼的心脏毒性水平较低。心脏事件通常无症状，导致LVEF可逆性下降，在接受和未接受蒽环类药物或曲妥珠单抗预处理的患者中发生率相似。
