OK. My reason is that within the Pseudo-progression group, the events (aka: real progression or death) took longer than expected.
In my opinion, no one would dare go forward without completing a certain number of events in this Pseudoprogression subgroup that is basically its own trial.
Why is this?
Several years ago, pseudoprogression was not recognized as it is today. Previously, it was confused with true progression (and still can be early on), and the fact that it represented a response to chemoradiation treatment going on was slowly accepted in the field. Pseudoprogression is a visible way to see that the chemoradiation is working (it's not a necessary observation but it is a clear indication). Moreover, after phase I/II trials with DCVAX-L, it was determined that dendritic therapy even boosted this already responding pseudo progression group to unimaginable responses above and beyond the chemoradiation which was already helping. (I'm intentionally leaving out bogging this down with info overload re: the 4 subtypes).
Now, because there really is no confusion, once pseudo progression is accurately distinguished from true progression, this group will need to be treated with DCVAX-L.
So look at how the trial protocol changed over the years, particularly the changes in 2011.
The pseudo Pseudo-progression group is now in the trial, but it does not include the prior thirty three patients, so it got a late start, and it probably only draws from the 72 patients added in 2011 along with the pseudo progression protocol changes found in clinical trial.gov.
Even though they are not part of the primary endpoint, think about ending the trial before events in the pseudo progression group occurred. You go to the FDA with less ammo? No way! You go with both groups.
If you did not do this you might also lose the ability to treat this subgroup, which I think makes up almost half of the responding patients (in a normal population), until another trial was completed. Think NWBO would do that??? No way!
Waiting for the pseudo progression group to reach their # event point (which I calculate to be about 19 patients) is absolutely necessary.
It's taking longer because I'm almost certain 90% of the true progression or death events has to come from the placebo group. Pseudo-progression patients are likely the very same type of DCVAX-L patients that are still alive today that were treated 10 years ago. But remember, the placebo group still receives chemoradiation, which means that those patients are even responding to the SOC treatment better than average! So getting approximately 19 events from this group takes time.
