Replies to post #124765 on NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

I guess the point I was trying to make is simply that, within the dose dense trial, the table versus the KM curves in that publication use different starting points. Other than adjusting for that, like you, I think the dose dense trial provides a helpful comparator or sounding board -- particularly but not exclusively the unmethylated MGMT group.

[Rkmatters]

Hi Branko,

I understand why you chose to use STUPP. I would hesitate to use it, as in all honesty, I think graphing the best case scenario for the placebo group is more realistic, given STUPP trial accrual was 2001-2003. And while I agree UCLA had exceptional care at the time, that same care is trickling down to other clinical institutions, even into clinical trials

-- UCLA data includes survival from the best team of doctors who were evaluating each patient before deciding on best approach -- from diagnostics to surgical to oncologist -a practice that is done at most institutions today. And so there is no official standard being applied at UCLA, its best care for patients. Whereas STUPP was standardized at least until progression. DCVax-L is standard as well, but it gets a different mix of patients (less tumor load, possibly higher KPM scores; and intend to GTR patients).

The difference between STUPP protocol data and UCLA's historical should be expected for several reasons:

-- better overall surgical care at
UCLA. Their survival numbers include use of intraoperative MRI. Even the Phase I/II was privy to that tool. Prior to using that surgical tool (take MRI image during surgery to see if there is residual tumor before they close a patient) it was common for surgeons to think they removed all the tumor (that they could), to leave 20% behind.

-- the STUPP study is an ALL comers trial. GBM Patients with more difficult tumors were included (metastatic). Per the research paper, the data procured was based on a 39% GTR rate; 17% biopsy only, the rest ST. And GTR performance rates was not judged by volume. It was a subjective measure of surgeons rating their own surgeries, so it's truly likely that the rate they reported.

-- the STUPP study didn't recognize early psuedoprogression. It was a condition at the time that showed up later as at the time TMZ was used mostly as an adjuvant. Initiation of TMZ upfront with radiation caused the pseudo phenomenon to show up earlier. As such, it is understood that had some of those patients been able to continue TMZ care, instead of being termed progression, the survival statistics may have improved.

-- the STUPP study does not include agents such as Avastin or repeat RT. Whereas, UCLA does.

-- the STUPP study likely has a lower rate of second surgeries (believe it was equal per arm but around 25%) than UCLA does in practice.

Lastly, while this Phase III study does remove pseudo, but it only removes those whose size fit "progression" on the Post RT MRI scan. Having said that, about 50% of the pseudo that do show up, show up within a month of chemoradiation. The rest show up within the 12 week window. But that Post MRI scan was very shortly after RT/TMZ, not quite 2 weeks. Therefore, probably only 30-40% of early Pseudoprogression were removed at most that might show up early IMHO; the rest are enrolled in. But since the trial initiates vaccine it might end up showing a lower pseudo (Indeterminate) rate since the trial may end up enrolling high GTR rate and T cells reduce disease and inflammatory with time (possibly even by Month 2 scan). Time will tell.

I hope that helps.