Caveat: Its still all good.
Just processing an alternative:
My prior thinking (recent connecting posts) were based on the pseudo-progression patients being randomized into the primary endpoint arm of the trial once real progression is ruled out. Since I am very confident that those tumor-pseudo progression patients who get retested approx. 12 weeks after chemoradiation and show no real progression are randomized and blinded (based upon some internet cancer boards I saw) an alternative trial design is that they might be placed into a separate arm but randomized, blinded unto themselves, not the primary endpoint related group.
So we could possibly have this alternative situation:
1. Arm 1 -- Experimental arm-- patients who showed no signs of pseudo or true progression up to 4 weeks post chemo/radiation get DCVAX-L.
2. Arm2 -- Control Arm -- patients who showed no signs of pseudo or true progression up to 4 weeks post chemo/radiation get placebo.
3. Arm 3 --Crossover Arm -- patients from arm 1 or 2 who truly progress after more than 4 weeks post chemoradiation or 12 weeks post
4. Arm 4 -- Experimental X -- pseudo-progression patients who ruled out further signs of progression through week 12 post chemo/radiation get DCVAX-L.
5. Arm 5 -- Control X -- pseudo-progression patients who ruled out further signs of progression through week 12 post chemo/radiation get DCVAX-L.
If the trial followed this set-up rather than the one I previously described, I believe the only 2 arms that would be used to determine the primary and secondary endpoint would be arms 1 and 2.
If this is the case, then we'd probably have less mesenchymal patients in arms 1 and 2. At first blush this might seem not as helpful because in one of her two phase 1 trials, Linda Liau found that mesenchymal patients responded well to DCVAX-l.
However, one needs to know that trial only had enough patients to compare mesenchymal and Proneural. The classic and neural subtypes were not represented specifically, and in the 2 patients where we know they were different from mesenchymal and pro neural, one lived over 50 months who was treated with DCVAX-L.
So, if we are looking at perhaps mainly the "classic" subtype to determine if DCVAX-L treatment meets its primary endpoint, we are still very likely in the same shape, because:
1. Linda Liau and other researchers noticed that in many smaller clinical trials, where chemoradiation had a strong effect (initially), it resulted in DCVAX and other dendritic therapies having much more profound efficacy.
*In my prior analysis, I reported that mesenchymal might respond somewhat more (judged against its own subtype) than Classic (does to its own subtype) to aggressive chemo/radiation. However, after more research I find that the both respond (rate of response) very well (initially) and there is no statistical difference. Proneural does not appear to respond at all, and neural responds in far fewer cases than classic and mesenchymal.
Linda Liau's theory is that the DCVAX-L dendritic cells are able to get better biomarker/antigen uptake where the in vivo tumor is no longer able to protect itself because it is weakened or dead.
2. In the large number of compassionate use cases and trial cases combined, there was an 80% response rate to DCVAX-L. Mesenchymal only makes up about 30% of the (4) subtype population. This means the other main responder to dendritic therapy, classic -- according to retrospective studies -- is also responding. Proneural does not repond to DCVAX-L in the research that I reviewed.
3. Linda Liau stated that where there was early-acute-progression, DCVAX-L was not effective. Those type of patients were excluded from this phase 3 trial.
4. If the trial design is more like the one in this post, the "no longer" pseudo-progression group (arms 4 and 5 above) would still provide further validation even though it would not be for a primary or secondary endpoint.
5. A retrospective analysis concluded that both mesenchymal and classic respond to dendritic therapy. This is just like the different chemoradiation effect among those two subtypes, so this bolsters Linda Liau's theory ( that dead or dying in vivo tumors provide DCVAX-L dendritic cells even better uptake of biomarkers/antigens).
6. Not all mesenchymal tumors would show pseudo-progression.
Therefore, those patients would be placed in arm 1 or 2 above.
