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Early Potential Seen With Immunotherapy in Glioblastoma, But Questions Remain

Laura Panjwani
Published: Friday, Aug 26, 2016

David Reardon, MD

David Reardon, MD

Initial findings from clinical trials separately exploring the safety and efficacy of immunotherapy agents nivolumab (Opdivo) and pembrolizumab (Keytruda) as potential treatments for patients with glioblastoma are promising, according to David Reardon, MD. However, checkpoint inhibition in this area requires deeper research. 

"We have treatments that can help our patients, but the problem is the durability of the benefit; sooner or later the tumor acquires the ability to no longer respond to what we are treating it with and becomes resistant,” said Reardon, clinical director, Center for Neuro-Oncology, physician, Dana-Farber Cancer Institute and associate professor of Medicine, Harvard Medical School. "Durable benefit is now being seen with checkpoint blockade in metastatic melanoma, lung cancer, and even potentially in renal cell carcinoma, and I think that is a very exciting aspect of these therapies that we hope will be achieved for our brain cancer patients.”

In an interview with OncLive, Reardon shares the early promise for immunotherapy in brain cancer and what preliminary findings have already shown regarding checkpoint inhibition. Additionally, he sheds light on the significance of vaccines in brain cancer, and how a combination strategy that both accelerates the antitumor immune response and diminishes immunosuppression may be the most effective option.

OncLive: What data have we seen regarding immunotherapy in brain cancer that you are excited about?

Reardon: A number of the immunotherapy trials had preliminary data presented at ASCO. The efficacy data of these studies had not matured sufficiently to be presented at ASCO, but there was some initial safety data that was presented for the CheckMate-143 study with nivolumab (Opdivo), a MEDI4736 study, and a KEYNOTE study with pembrolizumab (Keytruda). Some preliminary efficacy data were also recorded, and the main body of that is forthcoming. We might get some data by the end of this year or the first or second quarter next year.

We are very excited about these checkpoint inhibitors; PD-1 and PD-L1 targeting inhibitors. There is significant growing preclinical data using immunocompetent intracranial glioblastoma models that show that these 3 agents can have a significant benefit for animals with glioblastoma growing in the brain. It is always exciting to see preclinical validation that this intervention has some promise. It is a big step to then take it into the clinic and to validate it in patients, but at least in the preclinical models, there is very exciting data to support all of the trials that are ongoing in the clinic.

Is there any understanding at this point how immunogenic brain cancer is?

For glioblastoma, the most common primary brain cancer that adults get, in general the immune infiltrate associated with it is certainly in the lower end of the spectrum of cancers. A higher degree of immune infiltrate is typically referred to as a hot tumor microenvironment, while a lesser degree of immune infiltrate is typically referred to as a cold tumor microenvironment. Glioblastoma falls in the middle there, but probably more toward the spectrum toward colder or less immune infiltrate typically seen.

Another important factor looks at the mutational burden associated with different cancers as a factor that may predict how immunogenic they might be. Glioblastoma again falls toward the middle of the spectrum of cancers in terms of average mutational burden. It is not at the low end, but not at the very high end like melanoma or lung cancer—it is kind of in between. Most of the data are pointing toward glioblastoma being in the middle range toward immunogenicity, maybe favoring the lower side. But we know much of the standard treatments that we use, particularly radiation therapy, can significantly enhance inflammation within the tumor microenvironment.




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