Dept. of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, Germany.
Comprehensive Cancer Center Mainfranken, University of Würzburg, Germany.
J Clin Endocrinol Metab. 2020 May 1;105(5):1461-8. doi: 10.1210/clinem/dgz318.
Objective response of advanced adrenocortical carcinoma (ACC) to mitotane and cytotoxic chemotherapy regimen is only ~20% and early tumor progression is frequent. Previous clinical trials with oral multikinase inhibitors were negative, which has been attributed in part to inadvertent drug interaction with mitotane. Cabozantinib (CABO) is an inhibitor of c-MET, vascular endothelial growth factor receptor 2, AXL, and RET and approved for advanced kidney cancer, liver carcinoma after previous sorafenib, and medullary thyroid carcinoma.
To investigate the clinical efficacy and safety of CABO monotherapy in ACC patients.
Retrospective cohort study.
Three referral centers for ACC (Germany, United States).
Sixteen patients (13 female) with progressive ACC received CABO after previous mitotane in 15/16 and 3 (median, range 0-8) further systemic treatments. Prior CABO therapy, mitotane was discontinued in all patients. Mitotane plasma concentration was <2 mg/L in 7/16 patients and discontinued >12 months in 6 additional patients before CABO use. In 4/5 cases with available plasma samples, CABO concentration was in the expected steady-state range. Adverse events of grade 1/2 and 3 were observed in 13 and 3 patients, respectively, and consistent with the known safety profile of CABO. Best response was partial response in 3, stable disease in 5, and progressive disease in 8 patients. Median progression-free and overall survival was 16 and 58 weeks, respectively.
CABO monotherapy appears to be safe and effective as a monotherapy in advanced ACC after failing prior treatments. Therefore, prospective investigation of CABO in ACC patients is warranted.
晚期肾上腺皮质癌（ACC）对米托坦和细胞毒性化疗方案的客观反应仅约为 20%，且早期肿瘤进展频繁。先前的口服多激酶抑制剂临床试验均为阴性，部分原因是与米托坦发生意外药物相互作用。卡博替尼（CABO）是一种 c-MET、血管内皮生长因子受体 2、AXL 和 RET 的抑制剂，已被批准用于晚期肾癌、索拉非尼治疗后的肝癌和甲状腺髓样癌。
研究 CABO 单药治疗 ACC 患者的临床疗效和安全性。
回顾性队列研究。
三个 ACC 转诊中心（德国、美国）。
16 例（13 例为女性）进展期 ACC 患者在 15/16 例中接受了米托坦治疗后，在 3（中位数，范围 0-8）例中接受了进一步的全身治疗。在所有患者中，米托坦在使用 CABO 前均已停药。16 例患者中有 7 例的米托坦血浆浓度<2 mg/L，另有 6 例在使用 CABO 前米托坦停药时间>12 个月。在 5 例可获得血浆样本的病例中，CABO 浓度处于预期的稳态范围。13 例患者出现 1/2 级和 3 级不良反应，3 例患者出现 3 级不良反应，与 CABO 的已知安全性特征一致。最佳反应为 3 例部分缓解，5 例疾病稳定，8 例疾病进展。中位无进展生存期和总生存期分别为 16 和 58 周。
在先前治疗失败的晚期 ACC 患者中，CABO 单药治疗似乎是安全有效的。因此，有必要对 CABO 治疗 ACC 患者进行前瞻性研究。
