Core Evidence Open Access Full Text Article Ranjith Babu D Cor y Adamson Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA Rindopepimut: an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma open access to scientific and medical research Dovepress R E V I E w Abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and is universally fatal. Despite surgical resection, radiotherapy, and systemic chemotherapy, the median overall survival is less than 15 months. As current therapies are not tumor-specific, treatment commonly results in toxicity. The epidermal growth factor receptor variant III (EGFRvIII) is a naturally occurring mutant of EGFR and is expressed on approximately 20% to 30% of GBMs. As it is not expressed on normal cells, it is an ideal therapeutic target. Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. Phase I and II clinical trials have demonstrated significantly higher progression-free and overall survival times in vaccinated patients with EGFRvIII-expressing GBM tumors. Side effects are minimal and mainly consist of hypersensitivity reactions. Due to the efficacy and safety of rindopepimut, it is a promising therapy for patients with GBM. Currently, rindopepimut is undergoing clinical testing in an international Phase III trial for newly diagnosed GBM and a Phase II trial for relapsed GBM. Keywords: CDX-110, EGFRvIII, glioblastoma, immunotherapy, PEPvIII Core evidence clinical impact summary for rindopepimut for EGFRvIII-positive glioblastoma Outcome measure Evidence Implications and phase II Disease-oriented evidence Induction of cellular Preclinical, phase I (VICTORI: N = 12) Vaccination results in specific and humoral antitumoral activity towards immune responses (ACTIVATE: N = 18; ACT II: N = 22; EGFRvIII-expressing cells ACT III: N = 65) with no cross-reactivity with studies demonstrating the induction normal cells of EGFRvIII- responses Patient-oriented evidence Progression-free Multicenter phase II clinical trials survival (PFS) demonstrating significantly higher PFS compared to historic controls and previous phase III clinical trials when added to the current standard of care specific cellular and humoral immune – ACTIVATE (14.2 vs 6.3 months (matched cohort)) – ACT II (15.2 vs 6.3 months (historical cohort)) – ACT III (12.3 vs 6.3 months (historical cohort)) Significantly improves patient quality of life and overall survival (Continued) Core Evidence 2012:7 93–103 © 2012 Babu and Adamson, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 93 Correspondence: Cory Adamson Division of Neurosurgery, DUMC 2624, Durham, NC 27710, USA Tel +1 919 698 3152 Fax +1 919 684 5483 Email cory.adamson@duke.edu submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/CE.S29001