David Reardon, MD
Rindopepimut is the first immunotherapy to have shown a survival benefit in brain cancers, specifically glioblastoma, explains David Reardon, MD.
Data showcasing the agent's clinical activity were reported from the phase II randomized ReACT study, which examined the efficacy of rindopepimut plus bevacizumab for the treatment of patients with relapsed glioblastoma. At the 2015 ASCO Annual Meeting, 6-month data showed that patients who received rindopepimut plus bevacizumab had a median progression-free survival (PFS) of 27%, compared with 11% in the bevacizumab plus placebo arm. The 73 patients enrolled in the study had newly diagnosed, resected, epidermal growth factor receptor variant III (EGFRvIII) glioblastoma.
Overall survival (OS) in the study was 24% in the rindopepimut/bevacizumab arm, while the bevacizumab/placebo arm had an OS rate of 17%. Median OS was 1 year in the rindopepimut/bevacizumab arm and 8.8 months in the bevacizumab/placebo arm.
In the 6 months since ASCO, the ReACT data have matured and shown that patients who continued to stay on the combination of rindopepimut and bevacizumab had a 25% survival rate at 2 years, compared with a 0% survival rate of those in the bevacizumab and placebo arm.
In an interview with OncLive
, Reardon, clinical director at the Center for Neuro-Oncology, Dana-Farber Cancer Institute, discusses the ReACT study's findings and the potential of rindopepimut and other immunotherapy agents for the treatment of patients with brain cancers, specifically glioblastoma.
OncLive: What details can you share regarding the ReACT study?
: The ReACT study is looking at an immunotherapy intervention with recurrent glioblastoma. Glioblastoma is the most common primary cancer that arises in the brain, and it’s tumor type that we do not have good, effective therapies for. Our best standard-of-care can control the disease for about 7 to 8 months, and the average patients are, unfortunately, passing away within 1 year to 1.5 years. We have not been able to define better therapies, despite research and efforts that can improve outcome.
A subset of these glioblastoma tumors has been discovered to express a mutated protein on the surface of the cells called EGFRvIII
. We understand EGFRvIII
biologically to be a growth factor present on about 30% of glioblastoma tumors that is always activated. When active, it is driving the cellular proliferation and survival pathways. We know that this is a particularly challenging subset of glioblastoma tumors because of the over-activity of this mutated growth factor receptor.
Rindopepimut is a peptide vaccine that targets the specific mutation associated with the EGFRvIII
mutated growth factor receptor. A number of studies have shown it to demonstrate promising activity in newly diagnosed patients. Therefore, we reasoned to see if it helps when the tumor recurred after standard therapy.
The ReACT study was designed to see if rindopepimut could improve outcome in glioblastoma patients. The patients were randomized to receive either a placebo vaccine plus bevacizumab, the anti-angiogenic agent, which is approved for glioblastoma, or rindopepimut plus bevacizumab. The study enrolled 73 patients who were randomized 1:1 to the two treatment arms.
The study demonstrated that the patients who received the rindopepimut vaccine had a consistent improvement across all parameters of efficacy that were evaluated. Specifically, PFS was prolonged with rindopepimut versus placebo. The radiographic response rate and, importantly, the durability of those responses, was longer in the patients who received rindopepimut.
Patients in the rindopepimut arm also had a reduced corticosteroid requirement, which is a surrogate of quality of life because steroids can have a detrimental effect on the function and capabilities of patients. Most importantly, rindopepimut recipients had a statistically significant improvement in overall survival.
This is very important. This is the first randomized study ever in glioblastoma that has shown a benefit with any immunotherapy. As a bigger picture, this provides a proof of concept that immunotherapies can impact brain cancer, specifically here with glioblastoma. Our hope is that it will have an impact like it has had on melanoma, lung cancer, and other types of cancer.
What information have you gathered from the data in the follow-up to the ReACT study?
We presented this data initially at the 2015 ASCO Annual Meeting and, at that time, the data were not fully mature. Now, we have a mature follow-up and final data associated with this study. Data presented at ASCO were a survival benefit associated with the vaccine.