Randomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma
Randomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma
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DOI：
10.1007/s11060-016-2092-2
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发表时间：
2016-05-01
影响因子：
3.9
通讯作者：
Neyns, B.
中科院分区：
文献类型：
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作者：
Duerinck, J.;Du Four, S.;Neyns, B.
我们进行了一项随机、非比较、多中心、II期临床试验，以研究阿西替尼（一种对血管内皮生长因子受体具有高亲和力和特异性的口服小分子酪氨酸激酶抑制剂）在既往接受放疗和替莫唑胺治疗后复发性胶质母细胞瘤患者中的疗效。44名患者被随机分配接受阿西替尼（5 mg BID起始剂量; N = 22）或“医生最佳替代疗法选择”（包括贝伐珠单抗（N = 20）或洛莫司汀（N = 2））治疗。6个月无进展生存期作为主要终点。阿昔替尼治疗患者的6个月无进展生存率估计为34%（95%CI 14-54），最佳替代治疗患者为28%（95%CI 8-48）;中位总生存期分别为29周和17周。根据RANO标准，28%接受阿西替尼治疗的患者和23%接受最佳替代治疗的患者记录到客观缓解。在阿昔替尼治疗缓解时，85%的患者在PET成像上记录了胶质母细胞瘤对18F-氟乙基-酪氨酸（18F-FET）的最大摄取减少。阿昔替尼队列中基线时接受类固醇治疗的15例患者中，4例可停止皮质类固醇治疗，7例可逐渐减少皮质类固醇治疗。最常见的阿昔替尼相关a级千分之3不良事件包括疲劳（9%）、腹泻（9%）和口腔感觉过敏（4.5%）。我们的结论是，阿西替尼具有单药临床活性和可管理的毒性特征复发性胶质母细胞瘤患者。
We conducted a randomized, non-comparative, multi center, phase II clinical trial in order to investigate the efficacy of axitinib, an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the vascular endothelial growth factor receptors, in patients with recurrent glioblastoma following prior treatment with radiation and temozolomide. Forty-four patients were randomly assigned to receive treatment with axitinib (5 mg BID starting dose; N = 22) or "physicians best alternative choice of therapy" that consisted of bevacizumab (N = 20) or lomustine (N = 2). Six-month progression-free survival served as the primary endpoint. The estimated 6-month progression-free survival rate was 34 % (95 % CI 14-54) for patients treated with axitinib and 28 % (95 % CI 8-48) with best alternative treatment; median overall survival was 29 and 17 weeks, respectively. Objective responses according to RANO criteria were documented in 28 % of patients treated with axitinib and 23 % of patients treated with best alternative therapy. A decrease in maximal uptake of 18F-fluoro-ethyl-tyrosine (18F-FET) by the glioblastoma on PET imaging was documented in 85 % of patients at the time of response on axitinib. Corticosteroid treatment could be stopped in four and tapered in seven out of the 15 patients who were treated with steroids at baseline in the axitinib cohort. Most frequent axitinib related grade a parts per thousand yen3 adverse events consisted of fatigue (9 %), diarrhea (9 %), and oral hyperesthesia (4.5 %). We conclude that axitinib has single-agent clinical activity and a manageable toxicity profile in patients with recurrent glioblastoma.