Glioblastoma multiforme (GBM) is a very a difficult cancer to treat and, despite significant progress with new agents, improved imaging, and surgical techniques, 1-year survival rates are still very low. However, a recent study is offering new promise after research into a new vaccine derived from patient tumors has demonstrated prolonged survival times. The vaccine is also being combined with bevacizumab (Avastin®) in an ongoing large-scale, multicenter, randomized phase 2 trial.
“This particular vaccine for brain cancer has been in development for years. Evidence has shown that it is safe for [patients with] brain cancer and it has potential for a survival benefit when compared to historical controls,” said Andrew Parsa, MD, PhD, chair of the Department of Neurological Surgery at the Feinberg School of Medicine at Northwestern University, Chicago, IL.
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In the recently published phase 2 study of the Prophage Series G-200 vaccine, 41 patients with high-grade GBM underwent gross total resection of recurrent GBM and received a median of six doses of the vaccine. After 6 months, 90.2% of patients treated with the vaccine were alive; at 12 months, 30% had survived.1 These survival times compare well with outcomes using standard treatment for newly diagnosed GBM (radiotherapy combined with temozolomide). In a previous randomized phase 3 study, the 2-year survival rate was 26.5% with radiotherapy combined with temozolomide and 10.4% with radiotherapy alone.2
With the Prophage Series vaccine, patients are treated once weekly with the vaccine for 4 weeks after surgery, followed by bi-weekly injections. Each vaccine contains the ‘antigenic fingerprint’ of the patient’s particular cancer and is designed to activate the patient’s immune system to specifically target cancer cells bearing this fingerprint.
GBM results in frequent clinical complications which may include thromboembolic events, seizures, and significant neurologic complications. Dr. Parsa said that one of the advantages with this immunotherapy is its side-effect profile. “We see no side effects,” Dr. Parsa told ChemotherapyAdvisor.com. “We see some redness at [the] injection site, but by and large, it is well tolerated.”
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Dr. Parsa noted that GBM is the most common primary malignant brain tumor and is often resistant to standard therapies. He explained that many patients respond to chemotherapy, temozolomide, bevacizumab, and radiotherapy, but the vast majority of patients experience recurrent disease. Now, there is hope that a synergistic effect with a targeted antitumor immunotherapy and antiangiogenic agent (bevacizumab) will improve outcomes. The trial, now underway, combines the two treatments and is the largest brain tumor trial ever funded by the National Cancer Institute, as well as the largest vaccine study ever conducted with bevacizumab.
“This is still a very difficult disease and we don’t really cure patients with glioblastoma. Some patients live beyond 3 years but whether they are ever really cured is difficult to say. So, any new therapy is potentially promising,” said Gerald Linette, MD, PhD, associate professor of medicine and neurosurgery at Washington University School of Medicine, St. Louis, MO. “The nice thing about these immunotherapy approaches [is] that they tend to be nontoxic and they are well tolerated by the patients.”
Dr. Linette said that there is an urgent need to identify biomarkers and to develop prognostic tests that identify which patients may benefit the most from individual therapies. “Once you [experience treatment failure with] bevacizumab, there is really no standard treatment that is used by neuro-oncologists. We try chemotherapy but most of it is ineffective,” said Dr. Linette in an interview with ChemotherapyAdvisor.com. “Things have changed significantly for the better in the last 10 years. Until 2005, the standard of care was just surgery and [postoperative] radiotherapy, and now there has been significant progress made.”
References
- Bloch O, Crane CA, Fuks Y, et al. Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial. Neuro Oncol. 2014;16(2):274-279.
- Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996.
