Phase II Study of Axitinib in Sorafenib-Refractory Metastatic Renal Cell Carcinoma
Phase II Study of Axitinib in Sorafenib-Refractory Metastatic Renal Cell Carcinoma
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DOI：
10.1200/jco.2008.21.7034
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发表时间：
2009-09-20
影响因子：
45.3
通讯作者：
Dutcher, Janice P.
中科院分区：
文献类型：
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作者：
Rini, Brian I.;Wilding, George;Dutcher, Janice P.
目的研究阿昔替尼（一种口服的、强效的、选择性的血管内皮生长因子（VEGF）受体1、2和3抑制剂）在既往治疗（包括但不限于索拉非尼）无效的转移性肾细胞癌（mRCC）患者中的疗效和安全性。索拉非尼难治性mRCC患者接受起始剂量的阿西替尼5 mg，口服，每日两次。采用单组、单阶段设计估计客观缓解率（ORR）的主要终点，根据RECIST（实体瘤疗效评价标准）定义。次要终点包括安全性，反应持续时间，无进展生存期（PFS），总生存期（OS），和患者报告outcomes.ResultsOf 62例招募，100%已收到前索拉非尼，和74.2%已收到两个或两个以上的系统性治疗。53.2%的患者将阿昔替尼剂量调整至大于5 mg，每日两次，35.5%的患者将剂量调整至小于5 mg，每日两次。在62例可评价缓解的患者中，ORR为22.6%，中位缓解持续时间为17.5个月。中位PFS和OS时间分别为7.4个月（95% CI，6.7 - 11.0个月）和13.6个月（95% CI，8.4 - 18.8个月）。全因3 - 4级不良事件包括手足综合征（16.1%）、疲劳（16.1%）、高血压（16.1%）、呼吸困难（14.5%）、腹泻（14.5%）、脱水（8.1%）和低血压（6.5%.ConclusionAxitinib在既往VEGF靶向治疗（包括索拉非尼）难治的mRCC患者中具有抗肿瘤活性。毒性为轻度至中度，可管理。一项比较阿昔替尼与索拉非尼在既往一线治疗方案难治的mRCC患者中的随机、III期试验正在进行中。J Clin Oncol 27：4462-4468. (C)2009年美国临床肿瘤学会
PurposeTo investigate the efficacy and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 in patients with metastatic renal cell carcinoma (mRCC) refractory to prior therapies that included, but were not limited to, sorafenib.Patients and MethodsIn this multicenter, open-label, phase II study, patients with sorafenib-refractory mRCC received a starting dose of axitinib 5 mg orally twice daily. A one-arm, single-stage design was used to estimate the primary end point of objective response rate (ORR), defined by RECIST (Response Evaluation Criteria in Solid Tumors). Secondary end points included safety, duration of response, progression-free survival (PFS), overall survival (OS), and patient-reported outcomes.ResultsOf 62 patients recruited, 100% had received prior sorafenib, and 74.2% had received two or more prior systemic treatments. The axitinib dose was titrated to greater than 5 mg twice daily in 53.2% of patients, and 35.5% of patients had the dose modified to less than 5 mg twice daily. In 62 patients evaluable for response, the ORR was 22.6%, and the median duration of response was 17.5 months. Median PFS and OS times were 7.4 months (95% CI, 6.7 to 11.0 months) and 13.6 months (95% CI, 8.4 to 18.8 months), respectively. All-causality grade 3 to 4 adverse events included hand-foot syndrome (16.1%), fatigue (16.1%), hypertension (16.1%), dyspnea (14.5%), diarrhea (14.5%), dehydration (8.1%), and hypotension (6.5%).ConclusionAxitinib has antitumor activity in patients with mRCC refractory to prior VEGF-targeted therapy, including sorafenib. Toxicities were mild to moderate and were manageable. A randomized, phase III trial to compare axitinib with sorafenib in patients who have mRCC refractory to one prior first-line therapy regimen is underway. J Clin Oncol 27:4462-4468. (C) 2009 by American Society of Clinical Oncology