This is the 3rd of the 4 payments of $250K that we pledged toward this $1 million project. I still need help raising the final $250K! If anyone is interested in helping, contact me! (Al Musella, DPM   musella@virtualtrials.com)

 Congratulations to one of my favorite brain tumor centers!

 This is a relatively small trial but shows a huge effect supporting the use of Optune for Glioblastoma.  

In the big EF-14 phase 3 trial for newly diagnosed glioblastoma, the trial was stopped at the first interim analysis because it was obvious the Optune arm was doing so much better than the control group that it was unethical to continue withholding Optune from newly diagnosed patients.    The people running this study did not do that - they allowed it to go on for 5 years - knowing that they were withholding the best treatment.  Doesn't sound fair to me.

 Very interesting question.  The clinical trial for Regorafenib in recurrent gbm showed a small benefit over Lomustine. However, the control group of Lomustine did terrible compared to the large trial testing Lomustine.  In the Regorafenib trial, the control group of Lomustine had 5.6 months of overall survival.  In the Lomustine trial, the same type of patients had a median overall survival of 8.6–9.8  months.  The Regorafenin group had 7.4 months.  So although Regorafenib did better than the randomized control group it did not do as well as the Lomustine in the Lomustine trial.  

 However, reports from real world use of the drug  came in that said almost all patients get severe side effects and they did not see the benefit seen in the trial.  So what do you do?

 Obviously more research needs to be done hopefully to find if there are biomarkers that would push you toward Lomustine, Regorafenib or the combination.  Perhaps the best way would be for having all patients be followed in a registry so we can see how it works in the real world and correlate with biomarkers.  As in our brain tumor virtual trial project or our new Excelsior registry https://clinicaltrials.gov/ct2/show/NCT03793088?term=musella&draw=2&rank=4

 This is one of the biggest problems we have - the high cost of treatments.  This analysis found a small benefit to adding bevacizumab (Avastin) to Temodar for people with inoperable Glioblastomas.  However, because of the high cost of the drug, it was determined that is not cost effective.  They set the acceptability bar at $26,500 to add 1 year of life. This treatment worked out to $171,638 for each year of life added. Not even close.  

 This is a societal problem. I do not blame the drug companies, as the cost to develop a drug under our system is so high that to recoup their investment, the prices have to be high.  Without high prices, there would not be new drugs getting approved.  We need to change the system so that any researcher with a good idea could afford to bring a drug through the system to get approval - which not only will drastically lower the cost of new drugs but gives us a wider range of treatments to use.

 VB-111 is an experimental gene therapy.   Two papers came out at the same time with conflicting results.  This phase 1/2 study had very good results but was not as large or well designed as the phase 3 trial. mentioned in the next article.  They used the treatment in a few different ways with the best being using the VB-111 alone until progression, then continue VB-111 and add Avastin.      My thoughts are that most of the immunotherapy trials fail because they stop the treatment too soon. These treatments take time to work, and sometimes the tumor looks worse before it gets better.

 VB-111 is an experimental gene therapy being tested for use in recurrent Glioblastoma.  As I mentioned in the previous article, the results for the phase 1/2 trial came out on the same day as the results of the phase 3 trial. I do not think I ever saw that happen before.  The Phase 1/2 trial came out very good however, this failed to show any improvement of VB-111 plus Avastin randomized against Avastin alone in recurrent GBM.   If they had the results of the phase1/2 trial before they designed this phase 3 trial, they might have designed it differently as the phase 1/2 trial showed that using VB-111 alone until recurrence, then continuing vb-111 and adding avastin did much better than starting with VB-111 and Avastin at the same time.  This shows that adding combinations doesn't always improve the outcome. Everything needs to be tested and timing is very important.

I am still a fan of VB-111 but think it needs more work to find the optimal way to use it.  

This says that the dose of Avastin (high vs low) doesn't make much difference in outcome.   This is important not only for cost but I would assume cutting the dose in half would also decrease side effects. May be worth asking your doctor about this if you are on Avastin.

 There was a high chance of toxcicity - but the results look pretty good.  Might be worth trying to add lomustine to the standard of temodar and optune.

This is our #givingTuesday appeal!   The bottom line is that we have helped a lot of brain tumor patients directly - not only with our compassionate use program and copay assistance program, but by offering treatment suggestions, referrals to major centers and clinical trials, offering education via our online forums and our Brain Tumor Guide For The Newly Diagnosed, helped speed up approvals and funded a lot of quality research.  Our programs are critical to speeding up the search for the cure and to help patients deal with a diagnosis of brain tumor. We offer all of this at no cost to the patient, so we need YOUR help. We are only limited by funding. We have projects on the back burner just waiting for funding. We need $250,000 by the end of this year just to cover our compassionate use grant.   We have plans that require a few million dollars in funding, but every dollar helps and even small donations are appreciated.  Check to see if your employer has a matching grants program!

 This is the most exciting news for GBM treatments. It is a small trial but the results are unheard of.   Unfortunately it is only available in Japan right now but we are working on trying to get access.  We are discussing it in our forum: https://forum.virtualtrials.org/forum/brain-tumor-research/122-g47-delta-results-available-on-17thnovember

 Thank to Roberto Pugliese, PhD, who did the translation!  
If anyone else is interested in helping us translate to another language, contact me!  

 We added 2 new videes to our video library. This is the start of a project to make it easier to understand the clinical trials listings on our website.  Instead of just a jumble of words, you can click on the video link and have an explanation of what is involved in the trial, how it works, early results and more!  You can discuss them in our new discussion forum! 

 This is a small study and needs to be replicated but this might be the biggest advance we have ever seen. They reported a 1 year survival rate of 92% in recurrent glioblastoma.  This is unheard of. Typically they expect 15% 1 year survival.    The survival curve (compared to historical controls) is on our website at https://forum.virtualtrials.org/forum/brain-tumor-research/122-g47-delta-results-available-on-17thnovember  and it is very impressive.

 Unfortunately it appears as if this is only available in Japan.  We need to get this to the USA.

The treatment is a third generation oncolytic herpes virus and it seems to work in all types of cancers that they tried.  The clinical trial was terminated early because it actually works,

 I went to a lecture about this at the Society of Neurooncology conference this last week.   Of course we want to find the cure and fight hard, but there comes a time when it is unwinnable and it is time to stop.  There is a very hard conversation to have with your family and health care team before you get to that point.  This video explains it better than any other I have seen.  It explains the choices you have and how you can let the team know how you feel. There is no right or wrong decision - it depends on how you feel about the topic, but it really needs to be thought about BEFORE you need it.

 There was a lot of research on Optune presented last week at the SNO meeting!   You can see the list of abstracts when you click the link below.. the abstracts are available on the Neuro-oncology website at https://academic.oup.com/neuro-oncology/issue/21/Supplement_6   you can search for the abstract number from the list of presentations, but note they reuse the abstract numbers from year to year so when you search for a presentation, you get a list of results.  Look for the year 2019!

highlights:

Using Optune at the same time as radiation is now possible.  Too early to report results but it was safe.

 Adding Celebrex or a checkpoint inhibitor or Avastin or Lomustine  to Optune helps somewhat!  We need to find the best combinations.

 Very good results, but these are small studies. In the newly diagnosed group, 7 of 15 patients had a complete response. This is with unmethylated MGMT patients which is a much worse group than methylated.  The data on the recurrent GBM is not available but they describe the trial!

It is possible that Val-083 should be used instead of Temodar for MGMT unmethylated patients.  Val-083 is  similar to Temodar - it is a chemotherapy (but IV not oral), but works at a different part of the DNA strand so the MGMT repair enzyme can not undo the damage like it does with Temodar.  (A GMB patient with unmethylated MGMT produces a lot of the repair enzyme, making Temodar almost ineffective).

 This is another of my favorites.  This is an oncolytic virus.  This interim report, which is a small study,  for recurrent GBM patient, showed the majority of patients had benefit, and some had complete responses (tumor gone!) that were durable.  Median survival time was already 12.3 months - which should get better with time. Will keep an eye on this one!

 That is what we thought but it is nice to have proof!

 Amazing results.  For recurrent gbm, 1 year survival of 92% compared to 15% historical controls.