Good morning Umibe. I’m working today clinically but let me see if I can go through your post:
1. I think PFS won’t end up being an issue at all. I think it will pass on this mark; I believe those who progressed while on placebo will have found to be true progression and they will be shown to have gotten some advantage from DCVax after that progression and crossover to treatment but it will pale in comparison to what those on DCVax treatment group will be found to have as far as PFS. And those who progressed and did not crossover will make this even more clear. Further, pseudoprogression in the treatment arm will clear itself either way; if adjudication can show that the MRI did indeed appear to be pseudoprogression and not true progression, and/or those patients continued to live without progression (or indeed had decrease in the size of their tumors) it will be counted as a NON progression and as a long PFS.
2. Median OS; I think medians are meaningless these days and won’t have much effect in the end as it’s been shown over and over that a treatment can actually be behind SOC at the median before the long tail begins to show. However I do believe once the placebo group is separated from the blended data mOS will also be shown to have been successful, as you’ve noted with the blended/blinded data. And as I mentioned above the crossover issue I feel will have been solved with the long extension of the trial despite so many who claim they should have unblinded long ago.
As far as subgroups go I feel this is more or less the meat of the subject as to how much bang certain types of glioblastomas get from the treatment but as you mentioned in regard to Dr. Ashkan that even the worst prognostic tumor types appear to gain some advantage over SOC alone.
3. Yes, you’re spot on with this. The data will be used for all subsequent trials including combos and be the richest source ever for glioblastoma in my opinion. I don’t think there’s a Physician in this world, let alone a patient, who will not walk through fire for this treatment.
4. If you read the latest guidance by the FDA in December one can feel, if not an outright visualize, the influence of DCVax on the guidance. I would not for a moment doubt that NWBO may have had some hand in this. I also believe, when the smoke clears and the treatment is approved, we will find out that the clinical hold was something very absurd that had absolutely nothing to do with the science or the way the trial was being run. As a matter of fact I believe we’ll see that what was going on in Germany was being fought for in the US and the FDA was holding it down for a very dumb reason, perhaps even politically motivated in some fashion that we may never clearly know or understand.
As far as my statement regarding the Oncologists at my center; “knowing” is a word I backtracked on a bit because I don’t want to be accused of hyperbole or emotional bias. I have no idea how many patients were treated here, it may have been only a small number. What I do “know” is that the oncologists believe it works and not just from the patients they’ve treated. They are in contact with others and discuss the trial on an ongoing basis; they didn’t just do their part and move on forgetting about it. It’s a huge and exciting trial for them I feel.
