Gone for good.
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I am with you. Too bad the first-line NSCLC trial didn't use bavi + docetaxel + carboplatin. Maybe we'll see that one day.
Thurly, yes that is impressive indeed. The distinction I would make is that the second-line NSCLC
trial is the only randomized, placebo controlled, double bind study of bavi yet to date. Results can
always be dismissed by others if the trial is not of that type.
RRdog, I agree with all your ideas about the financial future directions. I think that if the MOS comes in
at anything over 2X control it will be a major breakthrough. It will immediately be questioned too.
This would be a major paradigm shift for the treatment of cancer. Immunotherapy will have been
shown to be the path to follow in the future. Note that for second-line NSCLC all the targeted therapies
tried so far have yielded nothing. This will come as a direct challenge to the gene centered approach
of the last 30 years with its endless numbers of mutations which lead nowhere.
Yes, that is a nagging concern. Hopefully the next quarterly conference call will answer that question if we do not hear before then.
None of the other trials showed statistically significant improvement in MOS over docetaxel alone.
Three of them showed equivalence to docetaxel and were approved as an alternative, see my
post # 80879. The three are pemetrexed, gefitinib, Tarceva. Since we are dealing with approval of the
drugs using phase III trials is appropriate.
Inclusion of the Shepherd et al, 2000 presents a problem because this compared best standard of care
(pain management) to docetaxel. At the time there was no approved treatment for second-line NSCLC.
So in this case the treatment arm was docetaxel, but instead I designate the docetaxel arm as the
control arm because after that all the control arms were docetaxel alone. That trial also led to approval of
docetaxel as the first drug approved for second-line NSCLC. If I exclude the Shepherd et al, 2000
trial and use the other 11 trials the mean is then 1.02 and the standard deviation is 0.20, not much different.
However, now the bavi + docetaxel estimate is 5.0 standard deviation units above the mean.
5-sigma is the threshold used to decide that the Higgs boson was actually discovered!
One more thing. From the 12 trials the mean of treatment/control MOS = 0.99, and the standard deviation = 0.23.
The estimate for the bavi + docetaxel trial is 2.03. This is, (2.03 - 0.99)/0.23 = 4.5 standard deviation units
greater than the 12-trial mean ratio of 0.99. Just an interesting point.
I see it as Ceasar's legion invading to overthrow the status quo.
RRdog, in the words of Julius Caesar "the die has been cast".
Thursday it will be 9 months since the last patient was enrolled in the second-line NSCLC trial. I have to now
assume that if the MOS has not yet been triggered then the MOS must be at least 12 months and
counting. Doubling the MOS is a real milestone. A few more days later it will be 10 months since the
last patient was enrolled in the first-line NSCLC trial. Since this is an open-label trial it would be good if
Peregrine would announce when the control arm MOS is triggered. Hopefully it already has been.
RRdog do you have any projections on the first-line MOS?
It wouldn't seem to be that difficult. From this IIb trial they will see which dose to use, probably 3 mg/kg,
and then enroll maybe twice as many patients to get enough statistical power to cover the bases.
If MOS is doubled that means you won't need a huge trial to show statistical significance.
They already have a network of sites they could re-use. What else is different for a phase III trial?
Oh yes, forgot that once the word is out that survival doubles then it should be much easier to fully
enroll the trial is less time.
Sounds like you have crossed the Rubicon. Good questions. Exciting times for sure.
I am saying the market has it backwards.
Jake, I thought that link you posted previously explained why the seemingly positive results were
viewed so negatively. It might work well, but for a small percentage of NSCLC patients, and that
fact was just made known to investors. So the potential just dropped by a large amount.
[/quote]Smaller and smaller potential 28-Jun-12 12:27 pm
1) 62% of ALL patients in the Ph 2 B trial were dropped…
http://finance.yahoo.com/news/synta-anno...
“At the time of this interim analysis, a total of 114 adenocarcinoma and 69 non-adenocarcinoma patients had been enrolled. Following a review earlier this year that determined low likelihood of benefit in the non-adenocarcinoma population, the trial was modified to enroll only adenocarcinoma patients. Results reported below are for adenocarcinoma patients only.
2) So in one fell swoop -- Gantespib’s applicability to ~60% of non-small lung cell cancers no longer applies…
http://en.wikipedia.org/wiki/Lung_cancer...
The non-small cell lung carcinomas (NSCLC) are grouped together because their prognosis and management are similar. There are three main sub-types: adenocarcinoma, squamous cell lung carcinoma, and large cell lung carcinoma.
“Nearly 40% of lung cancers are adenocarcinoma. This type of cancer usually originates in peripheral lung tissue.[11] Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers"),[7] adenocarcinoma is the most common form of lung cancer.[13] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.[14]
Squamous cell carcinoma accounts for about 30% of lung cancers. They typically occur close to large airways. A hollow cavity and associated necrosis are commonly found at the center of the tumor.[11]
About 9% of lung cancers are large cell carcinoma. These are so named because the cancer cells are large, with a lot of cytoplasm, large nuclei and conspicuous nucleoli.[11]”
3. Even out of this this ~ 60% smaller adeno-only population…..SNTA only trialed with
“Elevated LDH ~30%, mutant KRAS ~15-30% of all adeno” or expressed as actual patient numbers
“N=31 elevated LDH patients; N=20 mutant KRAS patients”
http://www.syntapharma.com/Documents/GAL...
So you have subgroup of subgroups and you have less than two dozen patients
Hmmmm…[/quote]
I don't see this person's point. The median is the median, and we know that it has been triggered and is < 6 months. The tail doesn't change that. The distribution of the enrollment will change when the control MOS was triggered, but not the fact that it is < 6 months. So if it was triggered on Dec 31, 2011, or Jan 31, 2011, what does it matter? I guess he means that the treatment arm estimated MOS will be less, but even so it has to be a fairly large number by now, such as > 10 months.
The same website states "Date of First Enrollment (India) 17/05/2011".
Just more obfuscation.
I did go to that website and found it is in India. I suspect that the date given as
"Date of First Enrollment (Global) 30/01/2011" refers to enrollment outside of USA, or is just not correct.
Mojojojo, I trust your judgement on this. I am trying to keep it toned down too,
and hope for the best.
Except the PR of May 21, 2012 said that the MOS had not yet been reached in either arm.
I interpret that to mean the median had not yet been reached, or triggered, and
not that 80% (or whatever number they are using) of the treatment arm had not yet died
and so statistical significance had not yet been reached. Which means that MOS
should be at least 11.6 months now.
RRdog, this is quite amazing. I have no doubt that accelerated approval is now
a distinct possibility. A doubling of the MOS, at least, that is unheard of.
Avid better get more reactors because they will be pumping bavi out by the ton.
Also, if it gets AA for second-line NSCLC there is nothing to stop oncologists from
using bavi + docetaxel + carboplatin for first-line NSCLC treatment.
Mojojo, so if I am reading this correctly then all of the control arm patients had
died by May 21, 2012 when the results were announced? Also, the MOS for the treatment
arm will be 12 months about July 5? Do you think the unblinding criteria could have
included the death of all the control arm patients?
Docetaxel can be used in first-line NSCLC along with cisplatin. From Sanofi-aventis:
"TAXOTERE® in combination with cisplatin is indicated for the treatment of patients with unresectable,
locally advanced or metastatic NSCLC who have not previously received chemotherapy for this condition."
From Wikipedia: Docetaxel is marketed worldwide under the name Taxotere by Sanofi-Aventis.
Annual sales in 2010 were Euro 2.122 billion (US $3.1 billion). The patent expired in 2010.
How do you think this might affect things, if at all?
It seems to me if the MOS of second-line NSCLC is doubled and given that it is a
randomized, double-blind, placebo controlled trial with 120 patients, and
that there is safety data on hundreds more patients from many other trials then
advanced approval would have a very good chance of getting granted. In that case
$50 million upfront seems way too small. How about $150 million?
Not going to happen. Antibodies don't usually survive going through the digestive track.
If you look at my post # 77572 I talked about how docetaxel, gemcitabine, and sorafenib all have
immunomodulatory properties. I think besides suppressing MDSCs docetaxel is also very good at
increasing the amount of PS expressed on the tumor vasculature. Maybe they should just try using
bavi + docetaxel on every cancer type.
RRdog, I commented on that possibility in post # 81846. It would indeed be a big wake up call for oncologists I would think.
You can't really know, but I would interpret this as a big push from June to October 2011 to enroll maybe
the last 20% of the patients. That would mean 80% were enrolled as of one year ago, and all of the
last 20% for almost 9 months now. Comments RRdog?
I thought we had decided that since the second-line NSCLC was now unblinded they could
release the MOS when it was triggered, and report the significance later when that was triggered.
Since the first-line NSCLC was open-label they can do the same for that trial.
Why they waited on the signal seeking trials I do not know, but the times have changed
and so I think they would want to report them sooner rather than later. Maybe they
were just being extra cautious with the signal seeking trials since they were the first phase II trials.
Thanks RRdog. Good work. My estimates rise with each passing week.
I am now looking for a doubling of the MOS.
Sunstar, when I read that in the PR that is exactly what I thought. If bavi + gemcitabine can equal the
efficacy of the FOLFIRINOX trial without all the added toxicity then it will clearly become the new SOC
for advanced pancreatic cancer. Next up is the liver cancer trial.
The keyword from the PR is "interim" survival data to be released. Remember that this trial started enrollment
on Jan 5, 2011 so there will be many patients who completed treatment over a year earlier by the end of this year.
It is a randomized open-label trial.
Some people still think the Sun orbits the Earth.
That is not what I meant. I mean maybe the BP is waiting until the MOS is triggered before
a deal is finalized and they won't be buying any shares until then, if then. Who can know?
What if the MOS has not been triggered yet? Maybe they are waiting for it.
Geo, a deal on lung cancer could get PPHM to $20-30 once Bavi gets approval, couldn't it?
You can sell then and the rest of us can keep hanging on for those splits and get a lot more. I first bought in
Aug 2005 and hold 20,000 now. I too always thought it could go to $100/share and it will if lung, pancreatic,
liver, breast, prostate cancers some day get approved. Off to work, this vacation is over.
I really think that only applies during the treatment phase of the trial, not now, and as I just said the trial was run
as a randomized, double blinded, placebo controlled trial.
This is my 15th, and last, allowed posting for the day. Never used them all up before. You all have a good evening.
Geocappy, the same thought crossed my mind, that could be it.
I guess we will just have to wait and see. However, it is not an open label trial with MOS as a primary outcome,
MOS was not listed as any outcome measure, so I don't see any restrictions. I'll have to side with FireFox here,
and hope you are wrong. As you said, knowing the value of the treatment MOS vs control could be worth a lot
in any deal making.