What is new in Brain Tumors?
November was the annual Society for Neuro-Oncology (SNO) meeting in San Antonio. This meeting is a four day meeting that involves educational activities and numerous research presentations. These presentations cover a wide range of topics from basic science studies (lab work, advances in genetic characterization of tumors), to preclinical studies in mice, to clinical studies in humans.
One of the most important presentation at the SNO meeting was a European phase III study in recurrent glioblastoma (GBM) of the combination of bevacizumab (Avastin) with lomustine (CCNU) versus Avastin alone. A previous phase II study had shown that the combination group had improved outcomes compared to the Avastin group. This led many neuro-onncologists to use the combination of Avastin and lomustine in many patients with recurrent GBM. In contrast to the phase II study, the phase III study showed no improvement in survival for the combination group. The reason for this is likely that the phase III study enrolled more patients and thus was better powered to show a difference. This outcome is practice changing in that it shows that there is still no proven therapy that can be added to Avastin to give better outcomes than giving Avastin alone.
Updates in Immunotherapy & Neuro-oncology
The theme of this year’s SNO meeting was immunotherapy. This is the hottest area of research now in neuro-oncology and other fields of oncology. The basic concept is that the immune system is disordered in GBM. The normal immune cells that fight off tumors are down regulated in GBM. This has been known for decades. What has not been known is how to turn on the immune response. Research over the past decade has led to important discoveries that are now being translated into therapies.
One important class of immune therapies is checkpoint inhibitors. These drugs down regulate a pathway called PD-1. The PD-1 pathway is turned on by the tumor and leads to down regulation of lymphocytes (immune cells). The PD-1 inhibitor, nivolumab (Opdivo) was used alone or in combination with Avastin in a trial in recurrent GBM. Not only did this trial show that the drug is well tolerated, but the patients had improved outcomes. It is important to note that this was a preliminary analysis. Other important immunotherapies include dendritic cell vaccines, chimeric antigen receptor vaccines, and viral vectors. Rindopepimut is a vaccine that leads to an antibody response to a mutant receptor that is present in about 20-30% of GBM patients. This vaccine has shown very promising results and likely will be FDA approved in the near future for this subset of patients. Additional promising data on rindopepimut trials was presented at SNO.
Another promising area in neuro-oncology is targeted therapies. One such target is the epidermal growth factor receptor (EGFR) which is overexpressed in more than half of patients with GBM. ABT-414 is an antibody drug conjugate that deliveries a toxin to GBM cells after binding to the EGFR. Data presented at SNO shows that this drug has shown significant responses in some patients with GBM. The drug will soon be launched into a phase II trial. Other targeted therapies continue to be under active investigation
Bright Future for Glioma Patients
The bottom line is that the future for glioma patients is bright. We are on the cusp of therapies that likely will make a substantial difference in the lives of patients. It is widely accepted that combination approaches are likely to lead to even better outcomes and eventually cures. The challenge is to find combinations of immunotherapies with targeted therapies and traditional therapies (radiation, temozolomide) that are effective and tolerated by patients.
Ryan T. Merrell, MD