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Abstract：
Background: Thyroid cancer is the most common endocrine tumor with an increasing incidence. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Surufatinib targets multiple kinases (vascular endothelial growth factor receptors, fibroblast growth factor receptor-1, and colony-stimulating factor-1 receptor) involved in tumor angiogenesis and tumor immune evasion. Surufatinib has demonstrated promising antitumor activity in various advanced solid tumors. This study aimed to determine the objective response rate (ORR) of surufatinib in patients with locally advanced or distant metastatic differentiated thyroid cancer (DTC) or medullary thyroid cancer (MTC). Methods: This Phase II open-label study by Simon\'s two-stage design was conducted at 10 sites across China. Patients with radioiodine (RAI)-refractory DTC with locally advanced disease or distant metastasis (DTC1 group); patients who received limited initial surgery and then developed locally advanced unresectable recurrences and were not considered candidates for RAI therapy due to residual normal thyroid tissue (DTC2 group); or patients with MTC with locally advanced disease or distant metastasis (MTC group) were enrolled. A total of 59 patients were enrolled (26 in DTC1, 6 in DTC2, and 27 in MTC) and received 300 mg surufatinib daily in 28-day cycles. The primary endpoint was ORR as determined by the investigators. Results: Overall ORR was 23.2% [95% confidence interval, CI 12.98-36.42]: 21.7% in the DTC1 cohort, 33.3% in the DTC2 cohort, and 22.2% in the MTC cohort. Forty-nine patients achieved disease control (87.5% [CI 75.93-94.82]): 87.0% in the DTC1 cohort, 83.3% in the DTC2 cohort, and 88.9% in the MTC cohort. Median time to response was 59.0 days, and 59.0, 85.5, and 59.0 days in the DTC1, DTC2, and MTC cohorts. Overall median progression-free survival was 11.1 months [CI 5.98-16.69]; 11.1 months in DTC1 and MTC cohorts, while the DTC2 cohort had not reached the median at the data cutoff. The most common treatment-emergent adverse events grade ≥3 were hypertension (20.3%), proteinuria (11.9%), and then elevated blood pressure, hypertriglyceridemia, and pulmonary inflammation (5.1% each). Conclusions: Surufatinib demonstrated promising efficacy with a tolerable and manageable safety profile for patients with locally advanced or metastatic MTC, RAI-refractory DTC, or locally advanced unresectable recurrences unable to receive RAI.
摘要：
背景:甲状腺癌是最常见的内分泌肿瘤,发病率逐年上升。晚期或复发性转移性疾病患者的治疗选择有限，导致预后不良。Surufatinib靶向多种激酶（血管内皮生长因子受体，成纤维细胞生长因子受体1和集落刺激因子1受体）参与肿瘤血管生成和肿瘤免疫逃避。Surufatinib已在各种晚期实体瘤中证明了有希望的抗肿瘤活性。本研究旨在确定局部晚期或远处转移性分化型甲状腺癌（DTC）或甲状腺髓样癌（MTC）患者使用舒法替尼的客观缓解率（ORR）。方法：通过Simon的两阶段设计，在中国10个地点进行了II期开放标签研究。放射性碘（RAI）难治性DTC伴局部晚期疾病或远处转移的患者（DTC1组）；接受有限的初始手术，然后发生局部晚期不可切除的复发，由于残留的正常甲状腺组织而不被认为是RAI治疗的候选人（DTC2组）；或患有局部晚期疾病或远处转移的MTC患者（MTC组）。共纳入59例患者（26例DTC1，6例DTC2和27例MTC），并在28天的周期中每天接受300mg苏鲁法替尼。主要终点是研究者确定的ORR。结果：总体ORR为23.2%[95%置信区间，CI12.98-36.42]：DTC1队列中的21.7%，DTC2队列中的33.3%，MTC队列中的22.2%。49例患者实现疾病控制（87.5%[CI75.93-94.82]）：DTC1队列中的87.0%，DTC2队列中的83.3%，MTC队列中的88.9%。中位反应时间为59.0天，DTC1、DTC2和MTC队列中的59.0、85.5和59.0天。总体中位无进展生存期为11.1个月[CI5.98-16.69]；DTC1和MTC队列为11.1个月，而DTC2队列尚未达到数据截止时的中位数。最常见的治疗引起的不良事件≥3级是高血压（20.3%），蛋白尿（11.9%），然后血压升高，高甘油三酯血症,和肺部炎症（各5.1％）。结论：对于局部晚期或转移性MTC患者，Surufatinib显示出有希望的疗效，具有可耐受和可控制的安全性。RAI-耐火DTC,或无法接收RAI的本地高级不可切除的复发。
