A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer.
A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer.
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一项多中心、开放标签、随机、II 期研究，研究西地尼布联合或不联合来那度胺治疗 131 碘难治性分化型甲状腺癌。
DOI：
10.1016/j.annonc.2023.05.002
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Vokes,EE
中科院分区：
文献类型：
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作者：
Rosenberg,AJ;Liao,C-Y;Karrison,T;deSouza,JA;Worden,FP;Libao,B;Krzyzanowska,MK;Hayes,DN;Winquist,E;Saloura,V;Prescott,K;Villaflor,VM;Seiwert,TY;Schechter,RB;Stadler,WM;Cohen,EEW;Vokes,EE
背景血管内皮生长因子受体(VEGFR)通路的多靶点酪氨酸激酶抑制物(TKI)在分化型甲状腺癌(DTC)中具有活性。来那度胺对DTC有初步疗效，但其与VEGFR靶向TKIs联合应用的安全性和有效性尚不清楚。在这项多中心、开放、随机、II期临床试验中，110例患者随机分为两组，单用头孢拉尼或联合来那度胺。主要终点是无进展生存期(PFS)。次要终点包括有效率、有效时间、毒性和总生存期(OS)。在一个多专科肿瘤委员会会议上审查的对进一步手术或放射性碘(≥)治疗无效的DTC患者(18岁)，在过去12个月内疾病进展的证据和不超过一种系统治疗的证据是合格的。头孢拉尼组和来那度胺组的中位PFS分别为14.8个月[95%可信区间8.5~23.8个月]和11.3个月(95%可信区间8.7~18.9个月)(P=0.36)。2年OS分别为64.8%(95%CI 43.3%~86.4%)和75.3%(95%CI 59.4%~91.0%)(P=0.80)。头孢拉尼布组和来那度胺组的严重不良事件发生率分别为41%和46%。结论头孢拉尼单药治疗RAI难治性DTC的疗效与其他VEGFR靶向TKIs相似，而来那度胺的加入并未带来临床上有意义的改善。
BackgroundMultitargeted tyrosine kinase inhibitors (TKIs) of the vascular endothelial growth factor receptor (VEGFR) pathway have activity in differentiated thyroid cancer (DTC). Lenalidomide demonstrated preliminary efficacy in DTC, but its safety and efficacy in combination with VEGFR-targeted TKIs is unknown. We sought to determine the safety and efficacy of cediranib, a VEGFR-targeted TKI, with or without lenalidomide, in the treatment of iodine 131-refractory DTC.Patients and methodsIn this multicenter, open-label, randomized, phase II clinical trial, 110 patients were enrolled and randomized to cediranib alone or cediranib with lenalidomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, duration of response, toxicity, and overall survival (OS). Patients (≥18 years of age) with DTC who were refractory to further surgical or radioactive iodine (RAI) therapy as reviewed at a multispecialty tumor board conference, and evidence of disease progression within the previous 12 months and no more than one prior line of systemic therapy were eligible.ResultsOf the 110 patients, 108 started therapy and were assessable for efficacy. The median PFS was 14.8 months [95% confidence interval (CI) 8.5-23.8 months] in the cediranib arm and 11.3 months (95% CI 8.7-18.9 months) in the cediranib with lenalidomide arm (P= 0.36). The 2-year OS was 64.8% (95% CI 43.3% to 86.4%) and 75.3% (95% CI 59.4% to 91.0%), respectively (P= 0.80). The serious adverse event rate was 41% in the cediranib arm and 46% in the cediranib with lenalidomide arm.ConclusionsSingle-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.