Research Strategies to Improve Outcomes in GBM



Andrew S. Chi, MD: One of the most important things in improving outcomes with patients with gliomas, in general, is to really apply all of the things that we’ve learned over the past 10 to 20 years—in terms of the biology of these tumors, and, specifically, the molecular subtypes and genetic subtypes of these tumors—in clinical practice and in clinical trials.

Again, I don’t think glioblastoma is one cancer. Glioblastoma is several cancers—probably 4 different very distinct molecular and genetic subtypes. We really have to study each one of these molecular subtypes in the lab, individually, distinct from each other. We need to treat these patients distinctly. With each of these subtypes, it is very likely that patients should be treated very differently. On the other hand, if you’re going to investigate the efficacy of your drug, you really have to test your therapy, whether it’s immunotherapy, drug therapy, or surgical therapy, on each individual subtype. It’s really tested on all glioblastoma. You really have a mixed bag of tumors. Some patients are going to do well and some patients aren’t. You really are not going to get a true sense of whether or not your therapy is working or not.

This is something that the field of glioblastoma is lagging in. We haven’t stratified patients enough for patient management, clinical care, nor clinical trials. Once we start doing that, that’s the first step. Certainly, novel immunotherapies or novel targeted therapies might come about. But unless you test them in the right populations, it would be very difficult to assess whether or not there’s going to be efficacy or not.

Because of all of this heterogeneity within what we call glioblastoma, some people would likely be overtreated, potentially. They may be exposed, unnecessarily, to toxicity, and may even suffer from that toxicity. They may even potentially die from the toxicity. And perhaps, in that particular molecular subtype—because they had a certain molecular subtype—they may have responded to standard therapy or done well, in general. They didn’t need to be exposed to so much toxicity. So, that’s one of the first major steps that I think we need to take, as a field, to improve outcomes in patients with glioblastoma.

The other thing that we need to do is take other factors, aside from survival, into account. What we’re doing with patients with glioblastoma is not just giving them chemotherapy, but we’re doing surgery to take out part of their brain, many times. And then, we are radiating their brain. Then, we look at outcomes such as the tumor coming back or how long the patient lives. But what is the quality of that survival? Some patients do extremely well with that multimodality therapy, and some patients really do not. Some people get severe cognitive impairment, motor impairment, from the treatments that we do. Some of the treatments that we are doing are directed at their brain.

We also need to start looking at measures aside from quality—neuropsychological measures, neurocognitive measures—to see what we are doing. Are we really improving the quality of their life or sustaining a good quality of life, no matter how long they live? That’s so critical, for these patients.

And then, on the other hand, yes, we do need better drugs, better radiation, better surgical therapies to extend the lives of these patients. At the end of the day, we really haven’t made much progress in the past 50 to 90 years. We have made small incremental improvements in the survival of these patients. We need newer therapies. I think immunotherapy is very promising. But the current iteration of immunotherapy, right now, remains to demonstrate how much of an impact we’re going to make in patient survival. I do think that some of these combinations will be successful. It remains to be seen which of these combinations will work, but I do think that, eventually, we’ll get there. But, again, we do need better therapies.

Transcript Edited for Clarity

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