Glioblastoma Patients Appear to Live Longer with Vaccine
Glioblastoma (GBM) patients appear to live on average almost twice as long when a new vaccine is added to standard therapy according to a newly published study.
Findings from the phase II, multicenter trial study has been published online in the Journal of Clinical Oncology.
Researchers at Duke University Medical Center and The University of Texas MD Anderson Cancer Center conducted the study to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease.
The study involved 18 patients newly diagnosed with GBM and a matched set of 17 patients who served as controls. Patients in both groups received surgery, radiation and the chemotherapy drug temozolomide. Patients in the vaccine group began receiving injections one month after completing radiation and stayed on the vaccine as long as it appeared to be working.
Adding the vaccine to standard therapy extended median survival time from an expected 15 months to 26 months. Patients in the vaccine group also experienced a much longer progression-free survival period, 14.2 months, compared to 6.3 months for those who did not receive the vaccine.
Glioblastoma is the most common form of brain cancer with roughly 10,000 new cases arising in the U.S. each year. The presence of EGFRvIII allows cancer cells to grow wildly out of control, seeding new tumors throughout the brain. Despite some advances in radiation and chemotherapy, the prognosis for patients with such tumors is grim; on average they live just over one year following initial diagnosis.
"About a third of all glioblastomas are fueled by a very aggressive cancer gene, called EGFRvIII; these tumors are the 'worst of the worst,'" said John Sampson, M.D., Ph.D., the Robert H. and Gloria Wilkins Professor of Neurosurgery at Duke.
"Our study showed that the vaccine eliminated all of the cancer cells carrying this marker in all but one of our study participants," said Darell D. Bigner, M.D., Ph.D., director of the Preston Robert Tisch Brain Tumor Center and the senior author of the study.
The EGFRvIII variant was co-discovered by Bert Vogelstein and Albert Wong at Johns Hopkins University and Bigner, at Duke.
Researchers found that the vaccine (variously known as CDX-110 by Celldex Therapeutics, and Rindopepimut (PF-04948568) by Pfizer) stimulated an immune response in approximately half of the patients who received it. Six patients developed EGFRvIII-specific antibodies and three developed T-cell responses.
The data suggest that these responses are linked to increased survival time, "but the numbers are so small that we can not conclude this with any degree of certainty," says Amy Heimberger, MD, co-lead investigator, from MD Anderson.
Scientists were also able to examine pre- and post-vaccination tumor samples from 11 patients and found that when their tumors recurred, 82% lacked immunoreactivity. Sampson notes this demonstrates that the vaccine had done its job in eliminating the most aggressive cells.
Sampson notes that the EGFRvIII vaccine may be worth further investigation because this growth factor is also found in other kinds of cancer cells, but not in normal tissue, making it a good target for intervention.
Bigner says that even though the study is small, the findings are intriguing and merit further study. "This appears to be a promising start, but the biological complexity of these tumors suggests that we may need multiple agents to attack additional markers of tumor growth or treatment resistance to be wholly successful."
"Immunologic Escape After Prolonged Progression-Free Survival With Epidermal Growth Factor ReceptorVariant III Peptide Vaccination in Patients With NewlyDiagnosed Glioblastoma"; John H. Sampson, Amy B. Heimberger, Gary E. Archer, Kenneth D. Aldape, Allan H. Friedman, Henry S. Friedman, Mark R. Gilbert, James E. Herndon II, Roger E. McLendon, Duane A. Mitchell, David A. Reardon, Raymond Sawaya, Robert J. Schmittling, Weiming Shi, James J. Vredenburgh and Darell D. Bigner; Journal of Clinical Oncology
Published online before print October 4, 2010, doi: 10.1200/JCO.2010.28.6963 JCO.2010.28.6963