Glioblastoma presents roadblock to successful immunotherapy

SEATTLE — Although advancements have been made in immune checkpoint inhibitors, tumors such as glioblastoma present a roadblock to successful therapy, according to a presenter at the 2022 American Academy of Neurology annual meeting.

“Inhibitors have really revolutionized oncology in the past 10 years with various different indications,” Priya Kumthekar, MD, associate professor at Northwestern University Feinberg School of Medicine, said during a presentation. “Unfortunately [with] glioblastoma, checkpoint inhibition has not quite made the same impact.”

Immune checkpoint inhibitors, such as CTLA-4, PD-1 and PDL-1, have been developed and approved in the form of new prescription medication for the treatment of various cancers and Hodgkins lymphoma, among others. However, glioblastoma remains one of the most potent and aggressive forms of brain or spinal cord cancer, for which treatments may slow progression but cures have yet to be found.

Kumthekar cited two studies released within the past year in which glioblastoma disrupted immunotherapeutic impact —CheckMate 143, a randomized phase 3 study, which compared nivolumab and bevacizumab in patients with recurrent glioblastoma. The other, was a randomized phase 2 study of nivolumab, with the addition of either a standard or reduced dose of bevacizumab for those with recurrent glioblastoma.

In both studies, Kumthekar said, there was no difference in overall survival between groups treated with either drug or different dosages, noting that advanced immunotherapy developments are likely to be driven by multifaceted treatment approaches, where understanding the unique tumor microenvironment and utilizing proper antigenic presentation and T-cell stimulation is necessary.

“We’re really looking at different immune cell populations in these environments, and we need to make sure that we’re treating our patients and designing our studies accordingly,” Kumthekar said. “We also need to understand the patient, and in doing so, if we have the right patient subset that are enrolled in studies, we can ensure that we maximize the potential that immunotherapy [provides].”

References:

• Reardon DA, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2020.1024.
• Ahluwalia M, et al. Neuro Oncol. 2022;doi:10.1093/neuonc/noz175.920.