Top Line: We know you (and everyone you know) are already familiar with the fanfare of the Duke poliovirus trial in glioblastoma multiforme (GBM). But today we’re bringing you the data, and we think it would make the most famous polio victim of all time proud.
The Study: Back in 2015, 60 Minutes ran a segment on this trial that uses an oncolytic poliovirus to treat recurrent GBM, and something about the approach resonated with the public. Perhaps it was the combination of a familiar medical marvel repurposed for a new, heroic mission. The therapy used in this phase 1 trial is called PVSRIPO, a vaccine strain of the poliovirus attenuated with a rhinovirus ribosome entry site to prevent virulence in healthy neuronal tissue. The virus gains entry into GBM cells via CD155 to induce a cytotoxic infection and an ensuing innate immune response, partly through the co-infection of antigen presenting cells. Following biopsy, 61 patients with a unifocal 1-5 cm recurrent GBM received escalating doses of PVSRIPO injections directly into their tumors, all preceded by a systemic polio vaccination. Rate of at least grade 3 toxicity was 20%, including one grade 4 intracranial hemorrhage at the highest vaccine dose. 2/8 patients with durable responses had a clinical complete response (CR), with an additional subset achieving a CR to subsequent salvage chemo. On imaging these responses produced initial FLAIR and enhancing progression followed by “soap bubble” cystic degeneration. Steroids were explicitly avoided in favor of bevacizumab to manage inflammatory symptoms. And now for the news headline because we occasionally like to bury the lead: the rate of overall survival for those followed to 36 months was 5/24 (i.e., an unbelievable 21%). Ultimately, the Kaplan-Meier curves say it all, or rather the small but poignant plateau that never falls to the x-axis.
Bottom Line: Intratumoral PVSRIPO for recurrent GBM appears to be safe and may even offer a miraculous therapy for a subset of patients who achieve durable tumor response. | Desjardins, N Engl J Med 2018