Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma
Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma
复制标题
DOI：
10.1007/s11060-017-2629-z
复制
发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Neyns, B.
中科院分区：
文献类型：
--
作者：
Duerinck, J.;Du Four, S.;Neyns, B.
阿西替尼是一种小分子酪氨酸激酶抑制剂，对血管内皮生长因子受体家族具有高亲和力和特异性。它先前已在一小群复发性胶质母细胞瘤（rGB）患者中证明了抗肿瘤活性。我们进行了一项非比较性随机II期临床试验，研究了rGB患者中阿西替尼单药治疗与阿西替尼加洛莫司汀（LOM）治疗的比较。主要终点为6个月无进展生存期（6 mPFS）。允许在阿西替尼单药治疗中进展的患者交叉。2011年8月至2015年7月期间，79例患者接受随机分组，并开始接受阿西替尼单药治疗（n = 50; AXI）或阿西替尼+洛莫司汀（n = 29; AXILOM）。中位年龄为55岁[范围18-80岁]，50 M/28 F。研究组之间的基线特征平衡良好。AXI组中19例患者在进展时交叉。治疗通常耐受良好。AXILOM患者发生3/4级中性粒细胞减少症（0 vs. 21%）和血小板减少症（4 vs. 29%）的风险较高。AXI组的最佳总体缓解率（BORR）为28%，AXILOM组为38%。AXI组和AXILOM组治疗患者的6 mPFS分别为26%（95% CI 14-38）和17%（95% CI 2-32）。中位总生存期为29周（95%CI 20-38）在AXI-arm和27.4周（95%CI 18.4-36.5）在AXI-arm。MGMT启动子高甲基化和类固醇治疗在基线与PFS和OS显着相关。我们从这些结果得出结论，阿西替尼改善反应率和无进展生存期rGB患者相比，历史对照。
Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB. Primary endpoint was 6 month progression-free survival (6mPFS). Patients who progressed on axitinib-monotherapy were allowed to cross-over. Between August 2011 and July 2015, 79 patients were randomized and initiated axitinib monotherapy (n = 50; AXI) or axitinib plus lomustine (n = 29; AXILOM). Median age was 55y [range 18-80], 50M/28F. Baseline characteristics were well balanced between study arms. Nineteen patients in the AXI-arm crossed-over at the time of progression. Treatment was generally well tolerated. AXILOM patients were at higher risk for grade 3/4 neutropenia (0 vs. 21%) and thrombocytopenia (4 vs. 29%). Best Overall Response Rate (BORR) in the AXI-arm was 28 vs. 38% in the AXILOM-arm. 6mPFS was 26% (95% CI 14-38) versus 17% (95% CI 2-32) for patients treated in the AXI versus AXILOM-arms, respectively. Median overall survival was 29 weeks (95% CI 20-38) in the AXI-arm and 27.4 weeks (95% CI 18.4-36.5) in the AXILOM-arm. MGMT-promoter hypermethylation and steroid treatment at baseline correlated significantly with PFS and OS. We conclude from these results that axitinib improves response rate and progression-free survival in patients with rGB compared to historical controls.