Options to Treat a Glioblastoma

Al Musella, DPM, President, Musella Foundation For Brain Tumor Research & Information, Inc., Hewlett, NY;
Email: musella@virtualtrials.com Phone: 888-295-4740

Q: You direct an established foundation that supports research and information about brain tumors. What would you do if you yourself were diagnosed with a glioblastoma multiforme (GBM)?

A: Now that GBMs are in the news again, I would like to discuss what I would do if it happened to me — an adult in otherwise good shape. There are several choices.

1. Standard of care: Surgery, radiation, Temozolomide. Chance of 5 year survival is about 5%.
2. Standard of care PLUS Optune. Bumps my chance of 5 year survival up to 13% with no added toxicity.
3. Phase 3 Clinical trials: There are only two phase 3 clinical trials for newly diagnosed GBM in the USA. The first, intraoperative radiotherapy may be worth trying, as it is a single application. However, there is only a 50-50 chance of getting the radiation, versus serving as a control. The other is using an off label immunotherapy drug, Nivolumab, which has previously failed as monotherapy, tested against Temozolomide in cases where Temozolomide is known to have little effect (unmethylated MGMT). Half of the patients will get Temozolomide in a situation where it is set up to fail. That is not acceptable to me especially since the Nivolumab is readily available off label outside of the trial without the risk of using an ineffective drug. (And using it off label opens up the possibility of combining with other treatments which may wind up working)
4. Phase 1 or 2 trials: There are about 100 of these trials in the USA. 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 which show results much better than the 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 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. Many of these trials will exclude you if you use Optune.
5. 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.
6. Cocktail approach involving experimental and 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 they tried and the outcome so we can learn from every patient. A Proposed New FDA Drug Approval Pathway: “Conditional” April 5, 2017 and More Details May 10, 2017

Getting Access to Experimental TherapiesThere 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. Last year, fewer than 1000 patients were able to get FDA approval to try experimental drugs under the FDA’s expanded access program. Getting multiple drugs this way for a cocktail is just about impossible. If the Trickett Wendler Right to Try Act of 2016 passes into law, it would make it easier to get these drugs. However, even if we could get them, without tracking the results, we are not learning and are doomed to repeating same failures.
Marty Tenenbaum and I previously wrote about our ideas for solving this problem. See https://virtualtrials.com/fda2017.cfm
So – bottom line: What would I do?

1. 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, and insertion of Gliadel wafer (intraoperative chemo therapy) 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).
2. Radiation – standard radiation or possibly proton beam radiation. Possibly followed by some type of boost. Possibly try adding a radiation enhancer like Trans Sodium Crocetinate – especially if there is residual tumor.
3. Temozolomide – during and after radiation. Only if the tumor sample has methylated MGMT. If the tumor is unmethylated, I would try to get Val-083 either in a trial or on compassionate use / right to try.
4. 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 you are being asked to gamble a known doubling of chances of 5 year survival for an unknown experimental treatment that might or might not help, and you might even be assigned to a control group. I would use Optune.
5. There are a few immunotherapies that have shown remarkable results in a minority of patients. A few of the early vaccine trials and the MDNA55 trial have tails of 20% or more of patients living over 5 years and with minimal or no side effects. The early Tocagen trials showed some impressive results. I would try to get one (or maybe 2) of these, and consider adding a checkpoint inhibitor. The polio vaccine trial (PVSRIPO) is getting a lot of hype on “60 minutes” with some very impressive results – but on a small number of patients, and a few serious side effects. I know the first patient in the trial, and she is doing great and tumor free 5 years after the treatment. It is hard to get into, but I would try. [Disclaimer: I am on the patient advisory board of the brain tumor center at Duke, and helped fund the PVSRIPO Trial].

What would you do?
Al Musella’s contact info is included in the author affiliations at the top of this page.
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