Checkpoint Inhibitors Show Promise in Glioblastoma

Allie Casey
Published: Friday, Nov 18, 2016

Finally, we're moving forward with a large registration study to evaluate pembrolizumab in the recurrent GBM setting that will be a large, randomized, phase II, multicenter, multinational study.

These initial results have really triggered a cascade of additional significant studies going forward, all the way to a planned registration study for this drug.

What has been learned thus far from the MEDI4736 trial?

This is a phase II clinical trial testing the PD-L1 inhibitor durvalumab in patients with GBM. It is a 5-arm study that includes 1 arm of newly diagnosed patients, and then 4 arms of recurrent glioblastoma patients. We're reporting on 1 of the arms for the recurrent GBM patients, involving 32 bevacizumab-naive patients who received single-agent durvalumab therapy. Again, similar to the KEYNOTE-028 pembrolizumab study, we saw a very well-tolerated side effect profile in patients treated with durvalumab.

In addition to the drug being well-tolerated in recurrent GBM patients, we also saw very encouraging efficacy results. The durvalumab study is the first PD-L1 inhibitor to be evaluated in patients with GBM, and there's been a lot of discussion of how a PD-L1 will compare relative to a PD-1 inhibitor. This is an important study to report out on that outcome.

What we have seen with this phase II study is that the results appear to be comparable to what's been reported with the PD-1 inhibitors. Specifically, we saw very exciting evidence of activity. Although there was a low rate of overall radiographic response, about half of the patients achieved stable disease with PD-L1 inhibitor therapy. What we saw in this study regarding PFS at 6 months was about 20% of the patients, which again is superior to historical benchmarks for recurrent GBM patients.

Even more exciting was the durability of this PFS in a subset of patients. All 6 patients who were progression-free at 6 months have remained progression-free for over a year. Some are at the 15-month mark and going strong. That again suggests there's this tail of the curve of a subset of patients who are having a remarkably durable benefit with this PD-L1–targeting immunotherapeutic for recurrent GBM.

This study is also looking at immuno-correlative biomarkers in the hope that we'll be able to better identify who are the patients more likely to benefit and who are maybe less likely. And, what can we potentially do to develop combinatorial regimens or other therapies to help improve their response rate and bring in a higher percentage of patients responding more durably?

What do these trials and new advances mean for oncologists and their therapeutic approach?

The KEYNOTE-028 and MEDI4736 studies are the first phase II trials reported on immune checkpoint inhibitors for glioblastoma patients. Both are in the recurrent setting which is always a challenging group of patients, but these findings indicate that the 2 agents appear to have a benefit and a role for this indication.

The medical oncology community should be paying attention to the development of immunotherapeutics for brain cancer and using the exciting results with these studies to be thinking about the development of immunotherapy for brain cancer. My hope is we'll see more and more studies validating the role of immunotherapy for brain cancer, as we have seen for melanoma, lung cancer, kidney cancer, and other cancer indications.

What do you think is the big takeaway from these trials?

The take-home message from the immunotherapy trials that have been presented here at the 2016 SNO meeting is that, very similar to other types of cancers, there appear to be a subset of patients with brain cancer who are also deriving significant benefit from these agents. Unfortunately, just as with other cancers, it seems to be a minority, but at least this research provides some exciting preliminary results and proof of principle that these agents can also have an impact on this cancer indication as well. It gives us data upon which we can build and move forward.

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