Institut Jules Bordet Institute and L'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
AC Camargo Cancer Center, São Paulo, Brasil.
Br J Cancer. 2020 May;122(10):1453-1460. doi: 10.1038/s41416-020-0786-x. Epub 2020 Mar 16.
Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting.
This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm.
With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68-1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4-11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF < 55% (vs > 64%, OR 3.1 [95% CI 1.54-6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25-2.75]), BMI > 30 kg/m (vs < 25 mg/kg, OR 2.21 [95% CI 1.40-3.49]), cumulative dose of doxorubicin ≥240 mg/m (OR 1.36 [95% CI 1.01-1.82]) and of epirubicin≥ 480 mg/m (OR 2.33 [95% CI 1.55-3.51]).
Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial.
ClinicalTrials.gov Identifier: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006-000562-36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2-06 /EGF106708/N063D.
曲妥珠单抗（T）是治疗人表皮生长因子受体 2 阳性（HER2 阳性）乳腺癌（BC）的主要药物，其导致的心脏毒性是最显著的不良反应。尽管 T 联合拉帕替尼（L）的双 HER2 阻断方案已在转移性环境中使用，但关于其心脏毒性的信息却知之甚少。
这是一项 ALTTO 试验的亚分析，该试验比较了早期 HER2 阳性 BC 患者的辅助治疗选择。符合条件的患者随机分配至 T 或 T 联合 L 组。根据治疗臂比较心脏不良事件（CE）发生率。
中位随访 6.9 年（FU），共纳入 4190 例患者，363 例（8.6%）发生 CE：T+L 组 166 例（7.9%），T 组 197 例（9.3%）（OR=0.85[95%CI，0.68-1.05]）。在抗 HER2 治疗期间发生 270 例 CE（6.4%），FU 期间发生 93 例（2.2%）（中位发病时间 6.6 个月[IQR=3.4-11.7]）。265 例 CE 为无症状（73%），94 例为有症状（26%），4 例为心脏死亡（1%）。301 例（83.8%）CE 患者得到恢复。确定的心脏危险因素包括：基线左心室射血分数（LVEF）<55%（vs>64%，OR 3.1[95%CI 1.54-6.25]）、糖尿病（OR 1.85[95%CI 1.25-2.75]）、BMI>30 kg/m（vs<25 kg/m，OR 2.21[95%CI 1.40-3.49]）、累积多柔比星剂量≥240 mg/m（OR 1.36[95%CI 1.01-1.82]）和表柔比星累积剂量≥480 mg/m（OR 2.33[95%CI 1.55-3.51]）。
从心脏角度来看，T+L 的双 HER2 阻断方案是一种安全的方案，但需要对患者进行心脏相关的详细病史采集以进行适当的患者选择。
ClinicalTrials.gov 标识符：NCT00490139（注册日期：2007 年 6 月 22 日）；EudraCT 编号：2006-000562-36（注册日期：2007 年 5 月 4 日）；赞助商方案编号：BIG2-06/EGF106708/N063D。
