I wrote a longer analysis earlier this weekend, but IHUB ate it.
So, I am going to give the short version.
Methylated MGMT is a subtype tumor that responds well (initially) to aggressive chemoradiation for GBM cancer -- the relationship is statistically significant and the response rate in these types of tumors is about 90%.
Studies strongly correlate Pseudo-progression patient's tumors with methylated MGMT. This relationship is also about 90%
As Linda Liau points out, there is a strong correlation between tumors that respond to chemoradiation, and tumors that respond DCVAX-L, such that they are synergistically related. Probably because DCVAX-L dendritic cells can uptake more biomarker/antigens from the dead andy dying tumor cells the resulted from the early aggressive chemoradion.
However, in the alternative possible trial design, the pseudo progression patients would not be used to determine the primary endpoint.
Question: Do the above points mean all the patients with methylated MGMT tumors are not included in the group of (probably) 240 patients being used to determine the primary endpoint -- under the possible alternative trial design?
Answer: No.
Reason:
1. The rate of methylated MGMT in GBM IV tumors is consistently about 45%.
2. The rate of pseudo-progression in GBM IV patients (based upon a huge comprehensive retrospective review of multiple studies) is about 18%.
3. The percent of methylated MGMT tumors in pseudo progression tumors is about 90%.
4. Therefore, based upon this info, there are only 16.2% of combined pseudo-progression/methylated MGMT in the overall GBM IV general tumor population.
5. Therefore, under the possible trial design I am considering in this post, if you took 240 patients x 45% methylated MGMT, you would have (approximately) 108 patients with methylated MGMT. This amount would be reduced by 16.2% x 240 = (about) 38.8 methylated MGMT patients that would otherwise be in the primary endpoint group, but were placed in a tertiary endpoint group instead.
6. Therefore, in trial arms 1 and 2 combined, there would be (about) 69.2 patients with Methylated MGMT out of the 240 patient pool -- if the patient population fell into global statistical averages.
Conclusion: I expect the primary endpoint pool in the phase III DCVAX-L trial to have a very robust percentage -- 29% -- of methylated MGMT patients. When combined with the fact that this pool excludes early acute real tumor progression (aka: chemoradiation non-responders and thus also less likely to respond to DCVAX-L according to Linda Liau and Dr. Kim), this primary endpoint pool should ultimately have very good responses to DCVAX-L for reasons stated in this and earlier posts.
Note: Because DCVAX-L has an 80% response rate, I certainly do not think it exclusively depends upon Methylated MGMT tumors in the patient population pool. However, Chemoradiation does rely very heavily (about 90%) upon Methylated MGMT patients. Thus there should be good separation between S.O.C. versus DCVAX-L plus standard of care. Thank heavens for the crossover arm.
