Department of Thyroid and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Clin Cancer Res. 2021 Jul 1;27(13):3567-3575. doi: 10.1158/1078-0432.CCR-20-2950. Epub 2021 Apr 8.
Medullary thyroid cancer (MTC) accounts for about 2% of all thyroid cancer, but has a relatively poor prognosis compared with differentiated thyroid cancer. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This multicenter, randomized, double-blind, placebo-controlled phase IIB study (ALTER 01031 and NCT02586350) was conducted to investigate the efficacy and safety of anlotinib in MTC.
Patients with histopathologically confirmed, unresectable locally advanced or metastatic MTC were enrolled and randomly assigned in a 2:1 ratio to receive anlotinib (12 mg once daily from day 1 to 14 every 3 weeks) or placebo. Patients in placebo group were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS).
Ninety-one patients were enrolled. At data cutoff date, the median PFS was significantly prolonged in the anlotinib group than in the placebo group (20.7 months vs. 11.1 months, = 0.029; HR, 0.53; 95% confidence interval, 0.30-0.95). The ORR of anlotinib treatment was 48.4%. The incidence of treatment-related adverse events (TRAE) was 100% and 89.7% in the anlotinib and placebo groups, respectively. The most common TRAEs of all grades in the anlotinib group were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%), and hypertriglyceridemia (48.4%).
Anlotinib demonstrates its efficacy and safety in this phase IIB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.
甲状腺髓样癌（MTC）约占所有甲状腺癌的 2%，但与分化型甲状腺癌相比，其预后相对较差。安罗替尼是一种新型的多靶点酪氨酸激酶抑制剂，靶向 VEGFR、PDGFR、FGFR 和 c-Kit。本研究为多中心、随机、双盲、安慰剂对照的 IIB 期研究（ALTER 01031 和 NCT02586350），旨在探讨安罗替尼在 MTC 中的疗效和安全性。
纳入组织病理学证实、不可切除的局部晚期或转移性 MTC 患者，以 2:1 的比例随机分配接受安罗替尼（12mg 每日 1 次，第 1 天至第 14 天，每 3 周 1 次）或安慰剂。安慰剂组患者在疾病进展后可接受开放标签安罗替尼治疗。主要终点为无进展生存期（PFS）；次要终点包括客观缓解率（ORR）、疾病控制率（DCR）和总生存期（OS）。
共纳入 91 例患者。截至数据截止日期，安罗替尼组的中位 PFS 明显长于安慰剂组（20.7 个月 vs. 11.1 个月， = 0.029；HR，0.53；95%置信区间，0.30-0.95）。安罗替尼治疗的 ORR 为 48.4%。安罗替尼组和安慰剂组的治疗相关不良事件（TRAE）发生率分别为 100%和 89.7%。安罗替尼组最常见的所有级别 TRAE 为手足皮肤反应（62.9%）、蛋白尿（61.3%）和高甘油三酯血症（48.4%）。
在这项 MTC 的 IIB 期试验中，安罗替尼显示出疗效和安全性，可能成为治疗这种罕见疾病的新选择，特别是对中国患者。
