Babu and Adamson Dovepress (Continued) Outcome measure Overall survival Safety Economic evidence Cost-effectiveness Evidence Multicenter phase II clinical trials demonstrating significantly higher overall survival compared to historic controls and previous phase III clinical trials when added to the current standard of care – ACTIVATE (26.0 vs 15.0 months (matched cohort)) – ACT II (23.6 vs 15.0 months (historical cohort)) – ACT III (24.6 vs 15.0 months (historical cohort)) Phase I (VICTORI: N = 12) and II (ACTIVATE: N = 18; ACT II: N = 22; ACT III: N = 65) studies demonstrating minimal adverse effects which mainly consisted of reactions that were not more severe than grade II toxicity Unknown as rindopepimut has not yet received marketing authorization Implications Significantly improves patient survival and supports its use for EGFRvIII-expressing glioblastoma multiformus Allows for the safe use in patients due to no evidence of significant autoimmunity as a result of vaccination Introduction Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. These tumors are classified by the World Health Organization (WHO) as grade IV gliomas and are highly aggressive, with recurrence occurring in all cases. Despite surgical resection, radiotherapy, and systemic chemotherapy, the median overall survival (OS) is less than 15 months.1 Additionally, patients with recurrent tumors have an even worse prognosis.2,3 While current therapies are able to increase OS and progression-free survival (PFS), these therapies damage normal tissue and typically fail.1,4,5 As a result, there is a need for more specific and effective thera- pies which are able to selectively target tumor cells without damaging normal brain cells. Immunotherapy has become an attractive therapeutic modality. The identification of tumor-associated antigens has allowed for the manipulation of the immune system to eliminate neoplastic cells without affecting normal paren- chyma.6 Currently, a variety of immunotherapies have been approved for the treatment of various cancers, with many in advanced clinical trials. These treatments are composed of cellular and recombinant components that utilize innate and adaptive immune responses. Immunotherapies consist of immune-modulating and tumor-specific antibodies, adoptive cell transfer, and cancer vaccines.7 94 submit your manuscript | www.dovepress.com Dovepress While tumor-specific monoclonal antibodies such as rituximab and trastuzumab are the highest grossing cancer therapies, there is increasing interest in the use of vaccines to activate the immune system against tumor antigens. One such target in GBM is the mutated epidermal growth factor receptor variant III (EGFRvIII), which is a tumor-specific epitope expressed on approximately 20%–30% of GBMs, 78% of breast carcinomas, 73% of ovarian carcinomas, 42% of head and neck squamous cell carcinomas, and 39% of non- small-cell lung cancers.8–14 EGFRvIII expression typically occurs in the presence of wild-type EGFR overexpression, occurring in 58% to 65% of such cases.8,15,16 As wild-type EGFR overexpression most frequently occurs in primary (de novo) GBM and rarely in secondary GBM (those that progress from low-grade tumors), EGFRvIII expression is most common in primary tumors.17,18 Also some studies have demonstrated a male predominance for EGFRvIII expression in GBM.8,19 While EGFRvIII has various oncogenic effects, its expression in GBM has not been seen to significantly affect survival compared to those who only express wild-type EGFR.8,16,19 EGFRvIII contains an in-frame deletion of 801 base pairs from the extracellular domain of EGFR, resulting in the fusion of two distant portions of the molecule (Figure 1). This creates an antigenic junction with a novel glycine residue.20,21 This constitutively active, Core Evidence 2012:7