A novel therapy has extended survival in glioblastoma patients far beyond the current median. After undergoing surgical resection and standard treatment, half the patients treated with the experimental vaccine in a small phase 1 study survived more than 5 years.
The usual median survival in such patients is around 15 months, but in this study, 7 of the 16 participants are still alive, with survival ranging from 60.7 to 82.7 months after diagnosis.
The findings were published earlier this year (Cancer Immunol Immunother. 2013;62:125-135) and were presented last month at the 4th Quadrennial Meeting of the World Federation of Neuro-Oncology in San Francisco.
It is striking that this many patients are still alive, said study author Keith Black, MD, chair of the Department of Neurosurgery and director of the Neurosurgical Institute at Cedars-Sinai Medical Center in Los Angeles. "Some patients are approaching 7 years, and 4 are alive without any sign of recurrence and living normal lives," he told Medscape Medical News. "Another patient has some signs of recurrence but is stable."
"I am not aware of any other trial that has had such dramatic results for glioblastoma multiforme," Dr. Black said. However, a question remains: "Is this just a statistical fluke, or is the mechanism of action of this vaccine really providing such a robust increase in survival?"
The experimental therapy, known as ICT-107, is an autologous vaccine that consists of a patient's dendritic cells pulsed with 6 peptides from tumor-associated antigens: AIM-2, TRP-2, HER2/neu, IL-13Ra2, gp100, and MAGE1. The vaccine is being developed by ImmunoCellular Therapeutics.
"One of the speculations is that the antigens are also targeting cancer stem cells, which may actually be part of the mechanism for the robustness of these results," Dr. Black explained. "We have also initiated 2 other vaccine trials at Cedars-Sinai targeting these cancer stem cells."
Survival Beyond 5 Years
The primary objective of the study was to determine the benefit of the ICT-107 vaccine in patients newly diagnosed with glioblastoma multiforme and to identify patients who survived longer than 5 years or who were disease free more than 5 years after receiving the vaccine.
The 16 study patients had undergone surgical resection and standard follow-up therapy with concurrent temozolomide and radiation. Only 4 patients did not undergo complete resection.
Patients were human leukocyte antigen serotype A1 or A2, and had at least 1 of the vaccine antigens present in their tumor. The vaccine was administered intradermally 3 times at 2-week intervals.
Median progression-free survival in the cohort was 16.9 months, and the 5-year rate of progression-free survival was 37.5%. Median overall survival was 38.4 months, and the 5-year rate of overall survival was 50%.
Eight of the 16 patients survived more than 5 years, and 7 are still alive (at 60.7, 65.1, 67.5, 67.4, 69.4, 77.9, and 82.7 months).
In 6 patients, progression-free survival has been more than 5 years. Four of the 6 continue to be disease-free at 65.1, 67.4, 77.9, and 82.7 months. One patient died of leukemia at 61 months, but the leukemia was not related to the therapy, Dr. Black explained. Another patient, who developed tumor progression at 62 months and underwent surgery and active treatment with temozolomide, is currently stable and doing well, he reported.
All of the long-term survivors had tumors with at least 5 antigens, and 75% percent had tumors with all 6 antigens. In addition, 100% expressed at least 4 cancer stem cell antigens (AIM2, TRP-2, HER2/neu, IL-13Ra2).
The secondary outcome of interferon-gamma response was significantly higher in those who survived at least 5 years than in those who did not (P = .0499).
Phase 2 Trial Underway
On the basis of this single-institution phase 1 trial, a phase 2 trial was initiated. "It is being conducted at 25 medical centers, and is randomized, placebo-controlled, and blinded," Dr. Black reported.
About 125 patients are now enrolled, and preliminary results will be released after 64 events, he explained.
"If the results are as good as the phase 1 trial, where we saw a very robust response, and if there is a greater than 9-month median survival increase, there will be a lot of interest in talking with the FDA about accelerated approval," Dr. Black said. "But if it is an intermediate increase, such as 3 to 4 months, we will be looking at a larger phase 3 trial."
Dr. Black reports owning stock in ImmunoCellular Therapeutics. Several members of the research team report ties to the company.
4th Quadrennial Meeting of the World Federation of Neuro-Oncology. Presented November 23, 2013.
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