ASCO: Vaccine Prolongs Survival in Glioblastoma Multiforme

A peptide vaccine, CDX-110 (Avant/Celldex, Pfizer), significantly prolonged survival in patients with newly diagnosed glioblastoma multiforme, when administered with temozolomide (Temodar; Schering). Results of a phase 2 study, conducted at Duke University and MD Anderson, were presented Monday at the annual meeting of ASCO. CDX-110 targets a tumor-specific mutation of epidermal growth factor receptor, EGFRvIII, which is present in one third to one half of glioblastoma tumors.

In the ACT II trial, 23 patients with resected glioblastoma underwent radiation and temozolomide therapy (75 mg/m2/d), followed by subsequent monthly cycles of temozolomide (200 mg/m2; n = 13) or continuous therapy (100 mg/m2; n = 8). Intradermal injections of CDX-110 were administered simultaneously. The overall median survival, 33.1 months, was significantly longer than that (15.2 months) in historical, temozolomide-treated matched controls. Time to progression,* 16.6 months, was also significantly longer (matched controls, 6 months).

The investigators reported 1 allergic reaction to the vaccine but no other serious adverse events. Temozolomide-induced grade 2 lymphopenia was experienced by more than half of the patients. Among the 11 patients who experienced tumor recurrence, only 3 exhibited EGFRvIII positivity—suggesting that tumor resistance occurs through an antigen-escape mechanism.

CDX-110 is under investigation in a phase 2/3, multicenter, randomized clinical trial and was granted fast-track status by the FDA in January. In an ASCO media briefing, MD Anderson oncologist Mark Gilbert said that Senator Ted Kennedy, who underwent glioma resection at Duke earlier this week, would qualify for the vaccine only if all of his tumor had been removed.

*Defined as a new, radiographically demonstrable lesion ≥1 cm in any 2 perpendicular planes.

Sagittal MRI demonstrating glioblastoma from Wikimedia Commons.