曲妥珠单抗治疗 HER2 阳性早期乳腺癌患者的心脏毒性发生率和心力衰竭协会-国际心脏肿瘤学会风险分层工具的验证。
Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer.
机构信息
Breast Unit, Department of Medicine, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, Surrey, UK.
Cardio-Oncology Service, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, Chelsea, London, SW3 6NP, UK.
出版信息
Breast Cancer Res Treat. 2021 Jul;188(1):149-163. doi: 10.1007/s10549-021-06192-w. Epub 2021 Apr 5.
PURPOSE
Trastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates [left ventricular ejection fraction (LVEF) decline, congestive heart failure (CHF), cardiac death or trastuzumab discontinuation] and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.
METHODS
Patients receiving curative trastuzumab between 2011 and 2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher's exact test, Chi-squared and logistic regression were used.
RESULTS
931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%). Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline ≥ 10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed. Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p = 0.002).
CONCLUSIONS
Cardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity.
目的
曲妥珠单抗可改善 HER2+早期乳腺癌患者的生存率。然而，心脏毒性仍然是一个关注点，尤其是在治愈性治疗环境中，并且临床试验之外关于其发生率的数据有限。我们回顾性评估了心脏毒性发生率（左心室射血分数 [LVEF] 下降、充血性心力衰竭 [CHF]、心脏死亡或曲妥珠单抗停药），并评估了一种用于预测常规临床实践中心脏毒性的模型的性能。
方法
确定了 2011 年至 2018 年期间接受治愈性曲妥珠单抗治疗的患者。记录了人口统计学、治疗、评估和毒性。使用 Fisher 确切检验、卡方检验和逻辑回归。
结果
931 例患者纳入分析。中位年龄为 54 岁（范围 24-83 岁），Charlson 合并症指数为 0（0-6），年龄在 65 岁或以上的患者有 195 例（20.9%）。228 例（24.5%）为吸烟者。608 例（65.3%）接受了蒽环类药物治疗。中位曲妥珠单抗剂量为 18（1-18）。401 例（43.1%）患者的 HFA-ICOS 心血管风险低，454 例（48.8%）患者的风险中等，70 例（7.5%）患者的风险高，6 例（0.6%）患者的风险极高。总体而言，155 例（16.6%）患者发生心脏毒性：141 例（15.1%）出现 LVEF 下降≥10%，55 例（5.9%）下降至 50%以下，42 例（4.5%）出现纽约心脏病协会 [NYHA] 心功能 II 级心力衰竭，5 例（0.5%）出现 III 级/IV 级心力衰竭，35 例（3.8%）因心脏原因停药。未观察到死亡。心脏毒性发生率随 HFA-ICOS 评分升高而增加（低风险 14.0%，中风险 16.7%，高/极高风险 30.3%；p=0.002）。
结论
在我们的队列中，心脏毒性较为常见（16.6%），但曲妥珠单抗治疗期间出现有症状的心力衰竭较为罕见。HFA-ICOS 评分可识别出发生心脏毒性的高风险患者。
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