Replies to post #209672 on NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

The idea of measuring from surgery is nonsense. The patients enrolled in the -L trial had no events prior to randomization. And YOU want to compare that to trials that did have events in those months.

Ex... if you've read any of long fellow's posts, he's made it abundantly clear and you'd be fully aware that he wants the trial to measure the control arm of L to the treatment arm of L, and that's the extent of it.

[longfellow95]

Well, Ex, on the Optune PFS, 6.7 months v 4.0 months, that calculates as a 67% improvement in median PFS for Optune.

If, however, you add on the median 3.8 months from surgery to randomization, then you would be looking at 10.5 months v 7.8 months. Which would be an improvement of 34.6%.
So two sets of figures for the same patients.
One appears to show an improvement in median PFS of 67%.
And the other set is 34.6%.
All depending on where you set the start line.
On this metric, the delta in favor of Optune appears a lot better if you go from randomization.

The shorter term OS milestone figures, and indeed median OS however, appear better if you measure from surgery.

In their final analysis, Optune treatment median OS was cited at 19.6 months, whereas DCVax blended OS is cited on both JTM and SNO figures as 23.1 months. Advantage DCVax. Until you subtract the 3.1 months which was the DCVax median time from surgery to randomization, and you get 19.6 v 20.0 months.
And so the true advantage on median OS to DCVax is very small.
But of course the DCVax figures are blended. And the advantage could be significantly bigger when we are talking about DCVax treatment only, after unblinding.

But I've never said anything otherwise.
I've said on several occasions that the Optune treatment and DCVax blended stats are neck and neck, until the DCVax long tail survival kicks in.

Reason enough to continue the trial until the long term survival advantage to DCVax over Optune turns from being a projected one to an actual one.
The Optune figures are also confounding because they have their interim figures which supported the approval (or label extension) and their final figures. And the final figures are a lot worse than their interim figures.
And then you have their two sets of figures, ITT and Per Protocol.
And then you have their website quoted figures that don't appear to tally with their official figures as submitted to the FDA!

The idea of measuring from surgery is not 'ridiculous'.
It's just that in making cross trial comparisons, you have to be aware of which trial is using which clock start, and adjust accordingly.
I don't believe DCVax is out of step with everybody else. I think there are other trials that also used diagnosis or surgery as the starting gun.
It would require someone with the time on their hands to look at other significant trials in the ndGBM space to check this out.
I guess these would include Stupp 2005, Brandes, maybe Rintega and one or two others for a full comparison.
But none of the past ndGBM P3's that I'm aware of, have better figures than what we are seeing in the DCVax trial.

And yes they all have slightly different inclusion/exclusion criteria, so any comparison will be imperfect anyway!

How about a trial of brain damage due to a gunshot to the head? I will randomize those who survive 1 week. I bet they do a hell of a lot better than those diver sees, even adjusting by a week.

Surely you are making my point here. The longer the gap between surgery and randomization, the more early progressors you exclude.
Optune had the longest gap of any trial I am aware of.

[longfellow95]

Wolfgang Wick didn't have much good to say about the DCVax trial, but he sure picked holes in the Optune one.

On the long gap before randomization:-

Patients had already experienced a favorable course of disease as the median interval between diagnosis and randomization was 3.8 months. The importance of timing is underscored by the fact that 82 of 1019 patients experienced progression in the (short?) interval between registration and randomization and were not randomized. In the EORTC trial5 coordinated by the same lead investigator, PFS was also measured from randomization but at a time close to diagnosis. At an interval of more than 3.5 months, more than 30% of patients had already progressed. Data from the Radiation Oncology Therapy Group 0525 trial, which also randomized the good-risk patients who were stable after radiotherapy, were used as a comparator. In this study, there was an almost 2-month difference in OS between registered and randomized patients.6 This time lag in the TTFields trial impacts the generalizability of the present data. As in other contemporary trials,7,8 it is not possible to decipher the risk factors for early progression. Age, resection, and MGMT status are comparable to trials in which randomization was closer to diagnosis. Thus, it will be difficult to define the group of patients that may derive benefit from present treatment or the exact starting time.

He levels many other criticisms of the trial and its validity.




https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767251/