My hypothesis is that the 23.1 month blended mOS from surgery as compared to the 15-17 months SOC from surgery is rather modest at first blush---20.1 months from randomisation and I would assume that you would need to subtract from the 15-17 months from surgery SOC marker to get to a randomised apples to apples comparison. The delta roughly remains the same even though the measuring stakes have changed. Anyway, this blended mOS does not tell the whole story.
From the blended data, we have seen the blended mOS results on methylated MGMT. In fact, it appears even in the case of unmethylated MGMT, that this blended mOS is quite striking in addition to methylated. I don't know to what extent MGMT+ and - correlate with mesenchymal but the expression of MGMT and mesenchymal appears to be different. One has to do with the on/off cellular repair switch and the other with the extent of the micro-tumour suppressive environment or how immunogenic the particular classification may be. Mesenchymal and MGMT may be additive and/or overlapping to some extent. It also appears that the vaccine may work to some extent on other classifications including classical(EGRFviii--there is some correlation seen with methylated MGMT) and the other two classifications, although I think the vaccine effect there is rather de minimis. This overall subgrouping is rather large and could be 40%-50% of the clinical pool of patients. You would think that this overall grouping would have a significantly more robust mOS than the blended mOS. And as Dr. Ashkans confirmed, DC VAX works across all groups[to varying degrees].
However, weighing down on this more robust mOS is the "placebo" arm composed of non-X and Xovers. Any extension of the X-overs would be relatively minor, I would surmise. Pure placebo and the population with little to no effect would also weigh heavily on the blended mOS in addition to X-overs. Thus, what appears to be a modest overall blended mOS, may really mean that the vaccine works extremely well in some subgroups but not so well in others and further, that it does not work very well for the X-overs(late treatment). In this regard, very few of the X-overs, I believe only three as reported by a MB poster, had resections. And recurrent GBM may manifest itself as a very aggressive mesenchymal strain(which is susceptible to DC VAX), extensive mutation from the original tumour(s)and with greater tumour load all these factors severely mitigating a significant positive effect on survival. Further, in these circumstances, one would expect to see some separation between the two arms.
As I explained in a previous post and at the risk of being repetitive, top line results just by the numbers may not be too meaningful by themselves. Good clear commentary will go a long way to prevent twisting what is good news into bad. I believe the spring refresh will not only confirm but overall will improve upon the already striking data we have seen in the publication.
Thus, I would conclude that the chances of success and ultimate approval by RAs are very encouraging. I also think that big P will see this and break ranks. This is digital. Either big or zero. I believe there are good odds for big. LP, and indeed all longs, may be able to go to a bigger home after all is said and done. Go big or go home indeed. JMHO.
