Department of Medical Oncology, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy.
Oncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy.
Br J Clin Pharmacol. 2019 Jun;85(6):1283-1289. doi: 10.1111/bcp.13895. Epub 2019 Mar 31.
Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients.
We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation.
The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72; P = 1.0).
This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected. Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms.
卡博替尼的心脏毒性数据不足。本研究的目的是评估卡博替尼治疗转移性肾细胞癌(mRCC)患者的心脏毒性风险。
我们对 2016 年 10 月至 2017 年 11 月期间接受卡博替尼治疗的 mRCC 患者进行了一项多中心前瞻性研究。在开始使用卡博替尼后 3 个月和 6 个月时,进行了经胸超声心动图和血浆生物标志物检测。
研究人群包括 22 名 mRCC 患者。基线时,9.1%的患者左心室射血分数(LVEF)降低,但均无左心室收缩功能障碍。基线时 LVEF 降低的患者在 3 个月后 LVEF 无明显进一步改变。6 个月后,仅 1 例患者的 LVEF 较基线下降>10%,导致左心室收缩功能障碍。基线时,64.7%和 27.3%的患者分别有升高的前脑利钠肽(proBNP)和高敏肌钙蛋白 I(hsTnI)。在基础正常 proBNP 和 hsTnI 的患者中,均无 3 个月和 6 个月时的升高值。基础升高的 proBNP 与基础降低的 LVEF 之间(P=0.29)和 6 个月后升高的 proBNP 与降低的 LVEF 之间(P=0.37)无相关性。同样,我们未发现升高的 hsTnI 与 LVEF 降低或基线时升高的 proBNP 之间存在相关性(P=0.47;P=0.38),也未发现与 3 个月(P=0.059;P=0.45)和 6 个月后(P=0.72;P=1.0)之间存在相关性。
这项前瞻性研究显示卡博替尼治疗相关左心室收缩功能障碍的风险适中。在不同时间点,升高的心脏标志物与降低的 LVEF 之间缺乏相关性。只有在出现临床症状时,才应保留对心脏功能的评估。