Rindopepimut Benefits Patients With EGFRvIII Mutation in Glioblastoma

The vaccine rindopepimut appears to benefit patients withepidermal growth factor receptor variant III mutation(EGFRvIII) in glioblastoma with regard to progression-free survival (PFS) and overall survival (OS). This group of patients has traditionally poor outcomes.

Evangelia Razis, MD, PhD, Hygeia Hospital, Athens, Greece, spoke of the compassionate use of rindopepimut in combination with other anticancer treatments at the Society for Neuro-Oncology (SNO) annual meeting in Miami Beach, Fla, on November 14, 2014.

Rindopepimut has a unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH). It is delivered intradermally with granulocyte macrophage colony-stimulating factor. The vaccine generates a specific immune response againstEGFRvIII-expressing glioblastoma, according to Razis.

The compassionate use study includes patients who did not qualify for enrollment in an open-label trial of the vaccine, she explained.

We're now presenting data from 64 patients treated at 23 sites in 6 countries, she said.

Patients included in the study had recently diagnosed and histologically confirmed glioblastoma, confirmed EGFR vIII mutation, previous or planned standard conformal radiation therapy with temozolomide, systemic corticosteroid use of 2 mg or less daily, and no autoimmune disease or concurrent conditions that would affect a patients ability to benefit from dosing.

Most patients received a monthly dose of rindopepimut after receiving an initial dose for 2-week periods.

Razis reported on data from 42 patients, 12 who had newly diagnosed glioblastoma that was resected or inoperable, and 30 with recurrent disease.

The median patient age was 53 years (15-70 years), and the median time from diagnosis was 14.5 months.O(6)-methylguanine-DNA methyltransferase(MGMT) methylation was present in 9/17; all patients tested were negative for isocitrate dehydrogenase-1 (IDH1) and IDH2.

Researchers found that rindopepimut was well tolerated when given in combination with temozolomide (57%), bevacizumab (57%), and other agents (17%). Treatment duration was a median of 3.7 months.

Many patients had mild reactions at the site of injection; one patient had serious cerebral edema that was thought to be treatment related, and another patient had a grade 1 headache. No patients had to discontinue therapy, although one patient decided to stop. Fourteen patients still use rindopepimut, according to Razis.

The median peak rindopepimut-induced anti-EGFR vIII titer was 1:1,200, according to the study abstract.

Tumor response indicated by more than 50% shrinkage was seen by researchers in 9 patients who had received the vaccine along with other agents. Three of the 9 patients had newly diagnosed glioblastoma, and 6 patients had recurrent disease. Eight of the 9 patients received recurrent temozolomide, and 4 patients received bevacizumab.

There was one patient who had complete response (CR) during treatment with several agents, including rindopepimut, erlotinib, temozolomide, and bevacizumab. This same patient has continued rindopepimut for more than 5 years with no recurrence of disease.

Another patient who received rindopepimut and temozolomide for approximately 9 months was shown on biopsy to have eliminated EGFR vIII mutation.

The median PFS was 9.1 and 2.5 months in in patients with newly diagnosed and recurrent glioblastoma, respectively.

Six patients had PFS for more than a year on treatment, Razis said. Three of those patients had newly diagnosed disease, while the other 3 had recurrent disease. Overall survival was 15.7 and 8.7 months from the first vaccination, respectively.

Rindopepimut is undergoing further investigation. The efficacy of rindopepimut is being studied in the ACT-IV trial, as well as in the phase II ReACT clinical study, data from which was presented earlier in the SNO meeting by David Reardon, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts. Researchers from ReACT found a 27% PFS at 6 months for patients receiving both the vaccine and bevacizumab compared with 11% for those receiving the control and bevacizumab.

Future research should also pair rindopepimut with bevacizumab, additional tumor antigens, and selected chemotherapy radiation, according to Razis.

Rindopepimut in combination with various anticancer therapies resulted in robust anti-EGFRvIIIhumoral response with minimal toxicity, she concluded.

Razis E, Vlahovic G, Recht L, et al. Vaccination against epidermal growth factor receptor variant III in glioblastoma: the rindopepimut compassionate use experience. Presented at the Society for Neuro-Oncology’s Annual Meeting. Miami Beach, Florida. November 14, 2014. Abstract IT-28

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