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Spin this.
A doctor (who sits with Dr Liau on the advisory board of the Musella foundation) discusses 3 failed immunotherapy trials. You're gonna love number 3.
Amazing..
I think AV must step forward and take credit for this rash of deletions.
Unintended Consequence of the Week Award!
Ah Cog Diss. You will forever have the satisfaction of knowing about books, and knowing what a bargain you got.
Have you noticed how anybody giving an expert opinion on YT from their lockdown study, always has an extensive book collection on shelves behind them? I think it is supposed to give a sheen of learnedness. I think they rent the shelves and books by the hour and get them wheeled in for the recording.
A couple of memory cards just doesn't cut it in quite the same way.
And when the lights and power all go down in a few months, you will be so glad of those weighty volumes during the long cold winter evenings.
HSpooner. I've not listened to all of it.
Does he really promote Avastin?
If he does, his judgement is seriously questionable.
And on the evidence of the P1, Direct has none of the toxicities associated with the ICI's. Keytruda is projected to be the top grossing drug in the world in a year or two, with over $20b sales per annum. And that is only one ICI.
Keytruda targets a range of solid cancers.
As indeed does Direct...
Bio. I think you missed something in my communication.
Ah, well, never mind...wasn't that funny.
(Well, I thought it was amusing. Ed.)
Yes; ICI's can also have Pseudo-progression as a response pattern: But don't mix up Pseudo-progression with Hyperprogression.
Two very different beasts.
On is usually a positive prognostic feature (when recognised).
The other one, ermmm, isn't...
mOS for GBM IS MORE THAN ONE YEAR ON CHEMO×Radiotherapy. So you are talking absolute nonsense when you must see the difference in weeks.
But that is good to know, so everybody knows you are purposely bashing, so we do not have to take anything you say into account.
A largely glossed-over finding from active-controlled trials of checkpoint inhibitors in solid tumors is the delayed crossover of Kaplan-Meier (K-M) survival curves, consistent with increased risk of disease progression and mortality early in checkpoint inhibitor immunotherapy (CPI). This raises the heretical proposition that CPI monotherapy may have a detrimental effect on progression and survival, early in treatment, relative to chemotherapy, in a significant number of patients.
An analysis across multiple solid tumors suggests this is not an uncommon finding. In an examination of data from 29 randomized controlled CPI trials, Winquist et al.1 found that CPI K-M survival curves violated proportional hazard assumptions more frequently than other anti-cancer monoclonal antibodies. This was characterized by early negative crossover of K-M survival curves opposing an overall beneficial survival trend or by delayed separation, an effect that can be large enough to negate any long-term survival advantage of CPI. This is a pattern that is evident across K-M curves from controlled trials of checkpoint inhibitors in several solid tumors, including gastric2, non-small-cell lung cancer (NSCLC)3, renal (favorable risk)4, head and neck5 and bladder6.
"Look at the Keytruda label, study the KM curves. You don’t wait years for real PFS or OS efficacy, you see it in weeks"
That'll be the hyperprogression.
How much were the bookshelves?
After Labor day...
That subpoena is likely driven by short complaints to the SEC.
Seems like you didn't listen to my post.
Fauci now acknowledging that vaccines are unlikely to prevent spread.
Remember all this was predicated on; 'no return to normal until we have a vaccine.'
"Dr. Anthony Fauci says chance of coronavirus vaccine being highly effective is ‘not great’"
The Food and Drug Administration has said it would authorize a coronavirus vaccine so long as it is safe and at least 50% effective. Dr. Stephen Hahn, the FDA’s commissioner, said last month that the vaccine or vaccines that end up getting authorized will prove to be more than 50% effective, but it’s possible the U.S. could end up with a vaccine that, on average, reduces a person’s risk of a Covid-19 infection by just 50%.
https://www.cnbc.com/2020/08/07/coronavirus-vaccine-dr-fauci-says-chances-of-it-being-highly-effective-is-not-great.html?fbclid=IwAR03dhKMInFW3mHjFrUlFspwR_P1Q780fm6CmLg8jLYt3EzkxkqW1I73ehg
What the hell use is that?
You could get the same effect by popping a few vitamins.
By contrast, collective immunity by natural transmission could be achieved in six months, but that is being actively prevented from happening. And then the whole thing would be over.
This virus just wants to be like the other millions of viruses, and peacefully co-exist with its host.
I'd love to believe we were in a "V" shaped recovery, but I believe we've made the mistake of opening too quickly, and that those schools that do reopen will be shut in a matter of weeks as they become the sight of major infectious spread of the disease.
I don't know precisely what percentage of our economy are providing services like waiters, trainers, hairdressers, etc, but I can't see the recovery approaching the employment levels prior to Covid-19 until all the people working in these largely service sector jobs can return to doing so safely in indoor venues. While it may be nice going to dinner outdoors in August, or having your hair cut, etc outdoors now, it won't be very comfortable doing so by October or November in many places. A recovery needs employment to be sustained, and that means moving businesses that have managed to move outdoors back indoors safely. I'm afraid this can't happen until we get the vaccine to the majority of American's and have enough experience with it to believe it's really effective. Hopefully by sometime in Spring of 2021 people will start to feel that some degree of normalcy has returned. I hope that SBA or someone will bankroll what previously were successful restaurant owners, gym owners, etc to reopen businesses that folded because of Covid-19 because they couldn't get the funds necessary to survive. It's hard to stay in business when there is no business, Govt. rightfully caused them to shut down as thousands were being infected when they were open, but they're desirable services once the fear is gone. I don't believe the owners of such businesses will have the resources to reopen unless the Govt. provides the seed money to do so.
I don't see why people have a high regard for an appearance on Cramer, while putting down a show like this.
By all means, feel free to take from it what you want.
But we already knew about 20 months ago that median survival of the Top 100 was about 5yrs: 58.4 months as reported at SNO.
And seeing as in reality, it was almost impossible for that median to go down, I would have expected it to stay the same or move up. With moving up being much more likely. If it were calculated right now, I would expect it to be at least 6yrs.
I doubt if they have ever formally calculated this median since SNO days. Because if they had, I would have expected Les to now be saying 'about 6yrs'
On the 85% / 25% thing; you're right. He might have meant 85% better than 25%. As in 46.25%.
JMO.
I'm not as confident as you Lykiri that something is moving in the UK.
But I don't discount the possibility either.
We know DCVax-L went through EAM's in the UK. Something that Remdesivir also did. Remdesivir has now gotten conditional approval (for Covid) from the EMA. And the MHRA will surely be following suit with some form of conditional approval for Rem in the UK, seeing as they have withdrawn the EAMs. I imagine NICE is in the process of producing a recommendation on Rem.
The difference with Rem (apart from the fact that it doesn't work) is that it did go through the EMA first.
But there is the chance that MHRA will want to show how expeditious it can be with drug approvals after the UK crash out of Europe at the end of the year. Could there be some real world data coming out of UK Specials that MHRA have indicated might support the P3 results?
Maybe.
Les did say they were getting good results from compassionate treatment, but he didn't say whether he was referring to UK Specials or US expanded access. He did say that the MHRA intend to have an accelerated programme after Brexit. But I don't think that is something that the MHRA have officially announced.
But when Les talked about approval in the UK in maybe 8 months he either knows more than any of us, or he giving us a line of bull!
We will see.
Yep, that worked. Thanks Marzan.
Lykiri. Do we actually have a YT link for the latest LG thing?
Thanks.
Does somebody get a free bonus knife set if they call in now?
Yes. Don't disagree Senti. It's just not a stat I've ever liked.
Actually, I don't know why I even thought it might be referenced in a topline release, when we are talking about unblinded arm by arm comparison. It won't be.
My apologies, Ex!
Perhaps I should have just said the entertainment and hospitality sector, which would include the wine and song.
Well, I suppose social distancing and the requirement for PPE was always going to have a negative impact on the personal services industry.
Whereas a gold tracker is proving a better safe harbour investment (as I predicted..), though a little mundane by comparison.
Well for sure, extending the trial was called for.
But KM makes the comparison based on events and censors non-events. Which is not ideal from their point of view, because you end up discounting your best treatment performers.
Those that haven't OS evented (or even PFS evented).
Which is where milestone stats such as OS36 or OS60 come in, because of the way that they focus on non-events i.e. percentage survival at the various timepoints.
And those sort of stats are just as legitimate, and have the advantage of being easily understood by physicians and patients in the real world, compared to a somewhat obscure hazard ratio. And you can still attach a p value to milestone arm by arm comparisons.
How is your alternative portfolio doing?
Plus the smaller than intended ITT, as I just mentioned to Sukus.
Take the two factors together, and the combined effect is not insignificant.
I guess I'm just observing this (again), plus the small inaccuracies in their data reporting.
I really hope they don't go down the Top 100 road when they are reporting topline. They will get ripped if they do.
Yes, I don't deny that Sukus.
If they had been able to achieve an ITT of 348 at 2:1, as they had planned, that would have been 116 controls.
But it is what it is, even if we don't know why it is what it is!
Not sure why you would think that particularly.
For any given ITT, the bigger the deviation from 1:1, the weaker the power.
There is a little squiggly thing in front of the 67%, otherwise known as a tilde, meaning 'approximately' or 'roughly' or 'more or less'.
(And now much used by devotees of emojis)
Which I suppose is a bit of a get-out.
Perhaps the intention is to make it a bit less obvious that the actual split was 70:30, a significant deviation from the protocol intention.
But why they would feel the need to do that, I don't know.
It's not the only anomaly. On the Top 100, it is stated on Slide 24, that 75% had a complete resection. On the next slide, it is 71%...
Not of any huge significance, but it's the sort of anomaly that they really need to avoid in the official trial outcome stats.
The AF's of the world will pore all over the final readouts, looking for any anomalies; so as to cast any doubt that they can on the data.
Thankyou Lykiri.
I will be subcontracting all my DD to you in the future.
I wonder about the 55k Euro price.
I wonder if that is for one round of treatment.
I find it hard to believe that is the total treatment price, somehow.
I suspect you are right, Doc.
Same guy presumably.
Any idea of the findings of the investigation?
He may just be a doctor / scientist who believes in his therapy, but hasn't got a few hundred million dollars (and 10yrs) spare, to go through a full trial process, and that's why he resents the whole BP status quo, so personally I won't jump to judge him.
We know that Laura from the UK is being treated at one of these clinics, probably this one. No recent update on the fundraising page, but the Facebook page suggests she is doing just fine at present, which is good news.
I'm thinking you may be located in Continental Europe.
No need to comment on that unless you wish to.
Regards.
Lykiri.
I think you are correct. Apologies for getting that wrong.
Though I believe both use the Newcastle virus.
Just came across a very recent paper by Van Gool, funnily enough.
IOZK call their DC therapy IO-VAC®.
From that paper:-
The vaccine IO-VAC® is normally produced by loading autologous DCs with oncolysate fromtumor cells derived from surgical resectates and thereof cultured cells. In many cases tumor specimens are not available due to inoperability or because the tumor had already been removed before considering immunotherapy. Therefore, IOZK is developing a technique of isolating tumor material from serum of patients. These are treated for five consecutive days with intravenous injection of oncolytic NDV in combination with mEHT via the Oncothermia EHY-2000 device (Oncotherm GmbH, Troisdorf,Germany). A new PanTum Detect assay evaluates by FACS analysis peripheral blood derived phagocytic monocytes/macrophages with ICD derived tumor markers using the Epitope Detection inMonocytes (EDIM) technology [28]. It revealed that during these five days of treatment ICD-induced tumor products are increasingly detectable in the serum. These are antigenic extracellular microvesicles and apoptotic bodies. Such serum material was used in case of the non-operable children with DIPG tumors to load their DCs
We retrospectively reviewed 132 cases of primary GBM. Multimodal immunotherapy was integrated as individualized treatment approach and following different scenario’s in combination with standard treatment in the first line treatment in 71 patients, used at time of first or subsequent relapse as treatment with or without chemotherapy in 61 cases. Median ages were resp. 55 and 53 y. Median KPI at start of immunotherapy was 90 and 80. Median OS for the patients treated with immunotherapy as part of first-line treatment was 20 months with 2-y OS of 40% (CI95%: -13,+13). Median OS for patients treated at time of relapse was 7 months with but still with 18-m OS of 16% (CI95%: -12,+9).
Just to add to the discussion on DC vaccines.
Jeannine Walston received a DC vaccine in Cologne long before she accessed DCVax-L. Don't think she was impressed...
https://jeanninewalston.com/integrative-cancer-care/body/other-integrative-cancer-approaches/the-truth-about-robert-gorter-md/
Jeannine as we know, went on to receive DCVax-L in 2014.
And I believe she is still doing well.
Several of these German clinics use some variation on a theme. Most use an oncolytic virus (usually Newcastle disease avian virus) as some sort of primer, with DC's cultured from PBMC's and some claim to be able to pick up antigens from an ordinary blood draw.
They seem to offer treatment even without tumor tissue available.
Though some may employ tumor tissue, but it is unclear how.
I think it is Dr Nesselhut at IOZK who has a fairly OK reputation.
But they all seem to lack the secret sauce.
I really don't know how the German clinics are licensed, but apparently they comply with GMP regulations.
It's why I don't worry if NWBO's patents aren't totally watertight, and it's true you can't claim exclusivity over using DC's, of course. But nobody has tried to accurately recreate or mimic L's process. Or if they have, they haven't achieved it. Extremely difficult I would say.
http://btcocktails.blogspot.com/2018/01/best-place-for-dendritic-cell-therapy.html
https://ascopubs.org/doi/abs/10.1200/jco.2011.29.15_suppl.2508
When half the independent or small chain restaurants across the US never re-open, that'll leave you with McDonalds, Burger King, and whatever your pizza chain is called.
And when the food shortage is imminent you can lay in a few thousand cheeseburgers without worrying about them going off.
https://www.bbc.co.uk/news/blogs-trending-50262547
So are you asserting that there has definitely not been an interim IA at all?
Why?
Does it put things in a better light somehow?
If so how?
Do you think anybody that says they think there was one is 'deceiving the board'?
Maybe they just disagree with you!
FWIW, I think there probably was one in 2015.
But hey, why does it matter, and why is it so important to you?
Bio, that conclusively demonstrates that there hadn't been an efficacy IA up until March 2014.
But it doesn't say anything about 2015.
I don't see why you need to argue that there wasn't one in 2015.
What does it matter?
An optimistic section of the board believe that there was one, and that because it was positive, that was why there was no further recruitment to control.
What's the point in arguing there wasn't one at all?
Can you please remind me when exactly Woodford stepped in, was it just post alleged peek?
August 17th 3pm.
Stick it in your diary.
May 22: Expect TLD Late June / Early July
June 29: TLD in "several weeks" and he pencils in Aug 3
Aug 2: TLD after Labor Day.
When this is through, it is very possible the US Dollar will no longer be the world’s preferred currency. People want their reserve currency to be from a stable country. When that happens, American life and the standard of living will change forever. That will be driven by how normal or insane we are as a country over the next year and months. We may recover, but there is no guarantee.