Dana-Farber Cancer Institute, Boston, Massachusetts.
Duke University Medical Center, Durham, North Carolina.
Clin Cancer Res. 2020 Apr 1;26(7):1586-1594. doi: 10.1158/1078-0432.CCR-18-1140. Epub 2020 Feb 7.
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.
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.
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 ( = 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 = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; = 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; < 0.0001).
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..
Rindopepimut 是一种针对肿瘤特异性 EGF 驱动突变 EGFRvIII 的疫苗。ReACT 研究旨在调查 rindopepimut 联合标准贝伐单抗治疗复发性 EGFRvIII 阳性胶质母细胞瘤患者的效果是否优于贝伐单抗单药治疗。
这是一项在美国 26 家医院进行的双盲、随机、二期研究（NCT01498328），入组的复发性 EGFRvIII 阳性胶质母细胞瘤患者为 bevacizumab 初治患者，随机接受 rindopepimut 或匙孔血蓝蛋白对照注射，同时联合贝伐单抗治疗。主要终点是中心审查的 6 个月无进展生存期（PFS6），单侧显著性水平为 0.2。
2012 年 5 月至 2014 年，73 例患者入组（rindopepimut 组 36 例，对照组 37 例）。rindopepimut 治疗的毒性包括短暂的低级别局部反应。主要终点是 rindopepimut 组的 PFS6 为 28%（10/36），对照组为 16%（6/37）（ = 0.12，单侧）。次要终点和探索性终点也有利于 rindopepimut 组，包括具有统计学意义的生存优势[HR，0.53；95%置信区间（CI），0.32-0.88；双侧对数秩检验 = 0.01]，更高的客观缓解率[30%（9/30）vs. 18%（6/34）； = 0.38]，中位缓解持续时间[7.8 个月（95%CI，3.5-22.2）vs. 5.6 个月（95%CI，3.7-7.4）]，以及至少 6 个月停用类固醇的能力[33%（6/18）vs. 0%（0/19）]。80%的 rindopepimut 治疗患者产生了强大的抗 EGFRvIII 滴度（≥1:12,800），与延长的生存时间相关（HR=0.17；95%CI，0.07-0.45； < 0.0001）。
我们的随机试验支持针对胶质母细胞瘤患者的靶向免疫治疗，但由于样本量小，以及复发性胶质母细胞瘤患者贝伐单抗反应的潜在异质性，治疗效果仍需要进一步验证。
