Adenovirus-mediated Gene Therapy with Sitimagene Ceradenovec Prolongs Median Time to Death or Reintervention in Adult Glioblastoma
In an open-label phase III trial (ASPECT) reported in Lancet Oncology, Manfred Westphal, MD, of University Hospital Eppendorf in Hamburg, and colleagues assessed the effects of locally applied adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir after surgical resection in patients with newly diagnosed resectable glioblastoma. They found that the sitimagene ceradenovec treatment significantly improved median time to reintervention or death but not overall survival compared with resection alone.
Study Details
The trial involved 38 European sites with recruitment between November 2005 and April 2007. In total, 250 patients aged 18 to 70 years with newly diagnosed supratentorial glioblastoma multiforme amenable to complete resection and a Karnofsky performance score ≥ 70 were randomly assigned to surgical resection of the tumor and intraoperative perilesional injection of sitimagene ceradenovec (1×1012 viral particles) followed by ganciclovir (postoperatively, 5 mg/kg IV twice a day) in addition to standard care (n = 124) or resection and standard care alone (n = 126). Temozolomide was not a standard treatment in all participating countries at the time of the study and was allowed at the discretion of the treating physician. The primary endpoint was the composite of time to death or reintervention, adjusted for temozolomide use.
Temozolomide was used by more patients in the control group overall (65% vs 49%) and among those with nonmethylated MGMT (67% vs 45%).
Significantly Longer Time to Death or Reintervention
Median time to death or reintervention was significantly longer in the sitimagene ceradenovec group (308 vs 268 days, hazard ratio [HR] = 1.53, P = .006). The effect of sitimagene ceradenovec was greater among the subgroup of patients with nonmethylated MGMT (HR = 1.72, P = .008). Sitimagene ceradenovec also increased time to death or reintervention among patients who never used temozolomide (HR = 1.58, P = .0398).
There was no difference between groups in overall survival (median, 497 vs 452 days; HR = 1.18; P = .31). There was evidence of a better effect of sitimagene ceradenovec treatment on overall survival among patients with nonmethylated MGMT, but the effect was not significant (HR = 1.40, P = .112). The 2-year overall survival rate was 25% in sitimagene ceradenovec group and 21% in the control group.
Adverse Events
More patients in the sitimagene ceradenovec group had one or more treatment-related adverse events of any grade (71% vs 43%). The most common grade 3 or 4 adverse events were hemiparesis (6.5% vs 2.4%) and aphasia (4.8% vs 1.6%). Treatment was discontinued due to an adverse event in 1.6% of sitimagene ceradenovec patients.
The investigators concluded: “Our findings suggest that use of sitimagene ceradenovec and ganciclovir after resection can increase time to death or reintervention in patients with newly diagnosed supratentorial glioblastoma multiforme, although the intervention did not improve overall survival. Locally delivered gene therapy for glioblastoma should be further developed, especially for patients who are unlikely to respond to standard chemotherapy.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
