Jung Wonyoung, Hubbard Rebecca A, Smith Amanda M, Ko Kyunga, Huang Anran, Wang Jessica, Isaacs Jordan M, Zhang Liyong, Liu Peter P, Chen Zhen, Shah Payal D, Mintzer David, Bhattacharya Saveri, Knollman Hayley M, Clark Amy S, Koropeckyj-Cox Daniel, Messinger Melissa, Wilcox Nicholas S, Xia Congying, Narayan Vivek, Upshaw Jenica N, Armenian Saro H, Ky Bonnie
Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA.
Breast Cancer Res Treat. 2025 Jun;211(2):293-305. doi: 10.1007/s10549-025-07636-3. Epub 2025 Apr 2.
Breast cancer treatment results in increased cardiotoxicity risk; a risk-guided approach to cardioprotection has not been fully tested.
This single-center, randomized Phase I trial enrolled patients with Stage I-III breast cancer who planned to receive anthracycline and/or trastuzumab therapy. An internally validated cardiotoxicity risk score classified participants as low or elevated risk. Elevated risk participants were randomized to receive open-label carvedilol or usual care for 12 months, beginning at cancer therapy initiation. Study visits occurred at baseline, 3, 6, 9, 12, and 24 months. Primary outcomes included feasibility, safety, and tolerability. Exploratory outcomes included echocardiography, biologic, and patient-reported measures.
Of the 166 eligible patients approached, 68 (41%) agreed to participate and ultimately enrolled. Among these participants (median age 52, 35% Black), 49 were classified as low and 19 elevated risk. Within the elevated risk group, 13 were randomized to carvedilol and 6 usual care. For those randomized to carvedilol, the median maximum dose was 6.25 mg twice daily, with 93% adherence. Adverse events of interest (grade 3 + bradycardia, hypotension, or fatigue) occurred in 9% with carvedilol, 13% in usual care, and 4% in low risk groups. One (1.5%) low risk participant experienced cardiac dysfunction. There were no substantial differences in secondary outcomes across groups. The participant withdrawal rate was 7%.
This Phase 1 trial demonstrates that a risk-guided strategy can be applied to patients with active cancer. However, additional strategies are necessary to optimize the design and execution of non-treatment intervention trials in patients with active cancer.
NCT04023110.
乳腺癌治疗会增加心脏毒性风险；一种基于风险的心脏保护方法尚未得到充分验证。
这项单中心、随机I期试验纳入了计划接受蒽环类药物和/或曲妥珠单抗治疗的I - III期乳腺癌患者。一个经过内部验证的心脏毒性风险评分将参与者分为低风险或高风险。高风险参与者被随机分配接受开放标签的卡维地洛或常规护理，为期12个月，从癌症治疗开始时起。研究访视在基线、3、6、9、12和24个月进行。主要结局包括可行性、安全性和耐受性。探索性结局包括超声心动图、生物学指标和患者报告的测量指标。
在166名符合条件的患者中，68名（41%）同意参与并最终入组。在这些参与者中（中位年龄52岁，35%为黑人），49名被分类为低风险，19名被分类为高风险。在高风险组中，13名被随机分配接受卡维地洛治疗，6名接受常规护理。对于那些被随机分配接受卡维地洛治疗的患者，最大剂量中位数为每日两次6.25毫克，依从性为93%。感兴趣的不良事件（3级及以上心动过缓、低血压或疲劳）在接受卡维地洛治疗的患者中发生率为9%，常规护理组为13%，低风险组为4%。一名（1.5%）低风险参与者出现心脏功能障碍。各组次要结局无显著差异。参与者退出率为7%。
这项I期试验表明，基于风险的策略可应用于患有活动性癌症的患者。然而，需要额外的策略来优化针对患有活动性癌症患者的非治疗性干预试验的设计和实施。
NCT0402
