Al Musella`s ASCO Highlights Part 1
Here are my thoughts on the most important abstacts so far. This is a first pass - I may add to this on our forum!
Let's discuss them in our forum - did I miss any? Let me know. Go to https://forum.virtualtrials.org/ to discuss these!
Posted on: 05/29/2020
Al Musella's ASCO Highlights
(In no particular order!)
- GAPVAC-101: First-in-human trial of a highly personalized peptide vaccination approach for patients with newly diagnosed glioblastoma. They reported median survival of 29 months for newly diagnosed glioblastoma on their first group of patients. Pretty good start!
- Survival benefit of tumor treating fields plus stereotactic radiosurgery for recurrent malignant gliomas. For recurrent tumors, Optune by itself is really not good enough - It is a slow, gentle treatment and needs time to work. It won't have time when the tumor recurs. Slowing the tumor down with stereotactic radiosurgery ( an easily available form of radiation you can have even after having the standard radiation) resulted in a median survival of 12 months combining the radiosurgery with Optune compared to 4 months with Optune alone. A major increase of 300%.
- Randomized phase IIb clinical trial of continuation or non-continuation with six cycles of temozolomide after the first six cycles of standard first-line treatment in patients with glioblastoma: A Spanish research group in neuro-oncology (GEINO) trial. This is a randomized prospective trial that tested 6 months vs 12 months of Temozolomide after chemoradiation. They found no difference in survival. An earlier study reported the same thing, and this confirms it.
- Efficacy of tumor treating fields (TTFields) in elderly patients with newly diagnosed glioblastoma (GBM): Sub-group analysis of the phase III EF-14 trial. This shows that the survival benefit even exists in the elderly.
- Temozolomide-induced hypermutation is associated with high-grade transformation, distant recurrence, and reduced survival after transformation in initially low-grade IDH-mutant diffuse gliomas. This may change the practice of using Temodar for IDH-mutant low grade gliomas. It shows that Temodar actually increases the chances of these benign tumors transforming into malignant tumors. The problem is what to change the treatment to. More research needs to be done to see if the alternative treatments do the same thing.
- INO-5401 and INO-9012 delivered intramuscularly (IM) with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma (GBM): Interim results. This is a new type of treatment to boost the immune system. They reported good results for MGMT unmethylated patients and will be presenting the results of MGMT methylated patient at the conference. For the unmethylated group, 1 year survival was 84%. They did not compare it to historical controls, but I see numbers like 50% reported elsewhere.
- Overcoming cell size escape from tumor treating fields using a varying frequency treatment paradigm in vitro. This is just in the test tube now and has to be tested in people but uncovers a possible explanation for why Optune doesn't just work on everyone for a long time. When exposed to the fixed frequency of 200kHz, cells of a certain size - if positioned correctly relating to the tumor treating fields - will not divide normally. One possible escape mechanism is that cells that tumor cells which are larger than the average are not as sensitive to that frequency - so the larger cells continue to grow and spread - or the tumor cells may just swell up in size. Verying the frequency to target those larger cells may be a way to make Optune work better!
- Tumor treating fields effects on the blood-brain barrier in vitro and in vivo This shows that Optune might open the blood brain barrier somewhat, making it easier for other treatments to get into the tumor. One negative is that it takes up to 96 hours to reverse this -which means that when you get contrast for your MRIs the contrast agent can get in better and make the scan look a little worse than it should.
- A pilot study of levetiracetam as a sensitizer of temozolomide for newly diagnosed glioblastoma: A prospective, open-label, phase II study (KBTS-1601 study). This is great news. Levetiracetam is an approved drug sold in the USA as Keppra - to control seizures - and it was found to enhance the effect of radiation therapy. This is a small trial and we should verify it in our registry, but they report an median overall survival of 30 months compared to historical controls of 17.5 months. Since many patients use anti-seizure medicine anyway, it may be worth using this drug during the radiation.
- MDNA55 survival in recurrent glioblastoma (rGBM) patients expressing the interleukin-4 receptor (IL4R) as compared to a matched synthetic control A single treatment for recurrent GBM who are not eligible for surgery shows a remarkable increase in survival of about 10 months compared to the standard options. This gives a new option for this worst subset of patients. Should be tested in newly diagnosed to see if it works even better.
- Clinical outcomes of the combination of bevacizumab and ttfields in patients with recurrent glioblastoma: Results of a phase II clinical trial. Optune by itself is not good enough for a recurrent tumor (as I mentioned in a previous entry). Optune needs time to work and a recurrent GBM patients doesn't have that time. They need something to slow down the tumor to buy the time needed. Adding Avastin to Optune for recurrent GBM resulted in much better results than that previously reported for Avastin alone or Optune alone! It may be worth trying the shot of stereotactic radiosurgery mentioned above, then combine Avastin with Optune. We will watch for that combination in our registry.
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