PURPOSE Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. PATIENTS AND METHODS In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. RESULTS Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32-0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5-22.2) vs. 5.6 (95% CI, 3.7-7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07-0.45; P < 0.0001). CONCLUSIONS Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.

中文翻译：

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Rindopepimut与Bevacizumab联合治疗表达EGFRvIII的成胶质细胞瘤（REACT）复发的患者：一项双盲随机II期试验的结果。

目的Rindopepimutmut是针对肿瘤特异性EGF驱动突变EGFRvIII的疫苗。ReACT研究调查了标准贝伐单抗中添加rindopepimut是否可改善EGFRvIII阳性胶质母细胞瘤复发患者的预后。患者和方法在美国26家医院进行的这项双盲，随机，II期双阶段研究（NCT01498328）中，将未接受贝伐单抗复发的EGFRvIII阳性胶质母细胞瘤的患者随机分配接受rindopepimut或对照注射匙孔血蓝蛋白，每次并用贝伐单抗。主要终点为中心评估的6个月无进展生存期（PFS6），单方面显着性为0.2。结果在2012年5月至2014年之间，有73名患者被随机分组​​（36名rindopepimut，37名对照组）。灵多比莫特的毒性包括短暂的，低度的局部反应。作为主要终点，rindopepimut的PFS6为28％（10/36），而对照的PFS6为16％（6/37）（P = 0.12，单侧）。次要和探索性终点也偏爱rindopepimut组，包括统计学上显着的生存优势[HR，0.53; 95％置信区间（CI），0.32-0.88；双面对数秩P = 0.01]，较高的ORR [30％（9/30）与18％（6/34; P = 0.38）]，中位缓解时间[7.8个月（95％CI，3.5） -22.2）vs. 5.6（95％CI，3.7-7.4）]，并且能够停用类固醇≥6个月[33％（6/18）vs. 0％（0/19）]。接受rindopepimut治疗的患者中有80％达到了强大的抗EGFRvIII滴度（≥1：12,800），这与存活时间延长相关（HR = 0.17； 95％CI，0.07-0.45； P <0.0001）。