Dr. Van Der Bent was an author on the original 2005 Stupp protocol trial and the follow up data in 2009.
As some of us discussed on the board back in the day, Dr. V’s trial was never blinded. They knew how to test for Methylation status and idh-1 status back then, but a huge chunk of the patients in the trial were undetermined or not tested in the status log. In other words, by todays standards, many did not have GBM (and had a much more favorable prognosis) and a huge proportion may have been methylated mgmt (a more favorable prognosis)
It was the equivalent of a phase ii trial because it had so many flaws. Phase two unblinded trials often have great results. After 20 years of the Stupp protocol, we know from many trials and real world data that long term survival is nearly nonexistent. We know Temodar interferes with tumor cell repair in methylated patients but that this is not durable. We also know Temodar in standard doses unfortunately exhaust T-cells and these are two of many reasons why its usage does not stop the nearly universal fatal prognosis for GBM.
I recently glanced at Dr. V’s critique of the Phase iii DCVax-l results. My first impression is that his apparent demand for a second phase iii trial is irresponsible and illogical. This is an orphan designated indication where the FDA required a crossover because his Stupp protocol trial therapy as now implemented is an eventual death sentence by itself. The phase iii trial for DCVax-l, unlike his old trial, was blinded during randomization and thereafter. When it became obvious PFS could not be used as an accurate endpoint due to pseudo progression, the trial remained blinded but was converted to utilize a concurrent ECA. The blinded trial tested for idh1 and methylation status. Unlike his unblinded trial, the DCVax-l trial was not padded. The trial resulted in unprecedented actual long term survival — not extrapolated.
Anyway, I’ll look at his paper further to address his other thoughts, but right now it’s Christmas.
