Two years ago, our Curious Dr. George asked Al Musella, DPM, what he would do if he were diagnosed with glioblastoma multiforme (GBM). Here, he revisits that question. Dr. Musella is President of the Musella Foundation For Brain Tumor Research & Information, Inc.
Curious Dr. George: You direct an established foundation that supports research and information about brain tumors. What would you do if you yourself were diagnosed with GBM?
Dr. Musella: Now that GBMs are in the news again, I would like to discuss what I would do if it happened to me—a newly diagnosed GBM in an adult in otherwise good shape. There are several choices:
Standard of Care: Surgery, radiation, and the drug temozolomide; with this standard approach, the chance of 5-year survival is about 5%. However, standard of care plus Optune—a wearable device that uses electrical fields to treat GBM—bumps my chance of 5-year survival up to 24.9% (if used over 90% of the time) with no added toxicity.
Phase 3 Clinical Trials: There are now about four phase 3 trials for newly diagnosed GBM in the U.S. One involves intraoperative radiation therapy at the time of the initial surgery and looks worthwhile. The others involve treatments that in earlier trials improved survival by just a few months. They may be worth a try if they did not have two big downsides: 1) Most have a control group of patients who receive the old standard of care so that some of the participants do not get the experimental treatment. 2) Some do not allow you to use Optune, so you are trading a known benefit for a chance at an unknown benefit.
Historically, over the last 50 years or so, only a handful of phase 3 trials have been successful. Optune was the most successful phase 3 trial, and no other phase 3 trial has yet come close, so the chances of doing better in a phase 3 trial than Optune is low. What we thought were the most promising phase 3 trials over the last few years all failed. We are waiting for results from the phase 3 trial of DcVax—that may be a game changer, but this therapy is not available to the public right now.
Phase 1 or 2 Trials: About 150 phase 1 or 2 trials are currently active in the U.S. There are many interesting choices here, but we do not have enough data to make an informed decision on which one to try. We do have early results from some phase 1 trials, some of which are better than those seen with standard therapies, but it is not likely that any one of these alone will make a big difference in survival for most patients. We do not (under the current system) have the ongoing results of these trials—we only get the results a few months after the trial is over. And while inside the trial, we cannot combine them with other treatments.
Off-Label Use of Drugs Approved for Other Diseases: There are many choices here, and a rational approach might be to select a “cocktail of drugs” based on a genomic analysis of my tumor.
Cocktail Approach Involving Experimental and FDA-Approved Treatments: Right now, this is impossible or very difficult to obtain. However, if it were possible, this would be my approach. Especially if we had a registry of all of the patients, the treatments tried, and the outcomes so we can learn from every patient.
Getting Access to Experimental Therapies: There are a few pathways to getting experimental therapies. Currently, none are really practical on a large scale. I have tried to get expanded access/compassionate use/right-to-try access on the most promising experimental treatments, and it is very hard. Getting multiple drugs this way for a cocktail is just about impossible. We had high hopes for the Right To Try Act, which was passed last year, but it turned out not to help at all. Drug companies are not willing to use this pathway for brain tumor patients. However, even if we could get them, without tracking the results, we are not learning and are doomed to repeating the same failures.
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So, bottom line: What would I do?
Surgery: I would begin with surgery, trying for maximal safe resection, possibly using Gliolan (a dye that helps surgeons see small clusters of GBM cells) to increase chances of maximal resection. I would also consider insertion of Gliadel wafer (intraoperative chemotherapy) if the resection cavity is not up against the ventricles (and we are not planning on entering a trial that excludes prior use of Gliadel) or some type of intra-operative radiation.
Radiation: I would receive standard radiation or possibly proton beam radiation. This may be followed by some type of boost, possibly “leading-edge” radiosurgery.
Temozolomide: I would receive this drug during and after radiation, only if molecular testing of my tumor sample detects methylated MGMT. If the tumor is unmethylated, I would seek treatment with the drug Val-083, either in a trial or through a compassionate use/right-to-try program. The length of time to use temozolomide is controversial. The most commonly uses length of treatment is 6 months after radiation (as well as during radiation).
Immunotherapy: There are a few immunotherapies that have shown remarkable results in a minority of patients. A few of the early vaccine and gene therapy trials have tails of 20% or more of patients living over 5 years and with minimal or no side effects. I would try to get one (or maybe two) of these drugs. The polio vaccine trial (PVSRIPO) looks promising, as does the CMV vaccine, the Survaxin vaccine, and Gliovac.
Optune: We are put into a very tricky situation here. Many trials will disqualify you if you use Optune, but Optune has the highest survival rates in large trials. So as I said before, you are being asked to gamble a known benefit for an unknown experimental treatment that might or might not help, and you might even be assigned to a control group. The results with Optune alone are still not good enough. The results shown above were for newly diagnosed GBMs. For recurrent GBMs, they are not nearly as good, so it is important to use it early in the course of the disease. Ideally, I would combine Optune with one of the immunotherapy treatments in phase 2 or 3, but that is not possible yet. We really need to fix that. Why should I be allowed to die just to appease an archaic tradition of requiring standard phase 2 and 3 trials?
…The choices are overwhelming for me. And for someone new to brain tumors, it is impossible to decide. We—the Musella Foundation—have formed a collaboration with Cancer Commons to create a program to help patients find the best treatment options for their individual case, then help them get access. We track how these patients do so that we learn from every patient. To take advantage of this free program, click here.
Dr. Musella can be reached at firstname.lastname@example.org.
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