Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial
| العنوان: | Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial |
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| المؤلفون: | Jennifer Green, Lynn S. Ashby, Gordon Li, Daniela A. Bota, Rimas V. Lukas, Tibor Keler, David A. Reardon, Louis B. Nabors, Karen Fink, Yi He, Laura Vitale, Scott Cruickshank, John H. Sampson, Thomas A. Davis, Christopher D. Turner, James J. Vredenburgh, David Tran, Donald M. O'Rourke, Annick Desjardins, Michael Yellin, Maciej M. Mrugala, J. Paul Duic |
| المصدر: | Clinical Cancer Research. 26:1586-1594 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Patients, Bevacizumab, Phases of clinical research, Cancer Vaccines, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Clinical endpoint, Humans, Medicine, biology, Brain Neoplasms, business.industry, medicine.disease, Confidence interval, ErbB Receptors, 030104 developmental biology, 030220 oncology & carcinogenesis, Vaccines, Subunit, Toxicity, biology.protein, Neoplasm Recurrence, Local, Glioblastoma, business, Keyhole limpet hemocyanin, medicine.drug |
| الوصف: | 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. See related commentary by Wick and Wagener, p. 1535 |
| تدمد: | 1557-3265 1078-0432 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e26132d50f0c31682e0aa28cebbf0fb7 https://doi.org/10.1158/1078-0432.ccr-18-1140 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e26132d50f0c31682e0aa28cebbf0fb7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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