Gone for good.
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Nothing wrong with your question. I would expect any data on either of the NSCLC clinical trials would
be presented at the annual ASCO meeting. The annual AACR (American Association for Cancer Research)
meeting is primarily devoted to basic and preclinical research, while the ASCO (American Society of Clinical Oncology)
meeting is mostly devoted to clinical results.
Abstract titles for 2013 AACR Annual meeting now on-line. I have found three so far.
http://www.abstractsonline.com/Plan/browse.aspx
Complete abstracts available on March 6.
Abstract Number: 2850
Presentation Title: Predicting anti-tumor responses to phosphatidylserine targeting antibodies using tumor imaging
Presentation Time: Tuesday, Apr 09, 2013, 8:00 AM -12:00 PM
Location: Hall A-C, Poster Section 21
Poster Board Number: 22
Author Block: Jian Gong1, Richard Archer1, Van Nguyen1, Christopher C.W. Hughes2, Jeff Hutchins1, Bruce Freimark1. 1Peregrine Pharmaceuticals, Inc., Tustin, CA; 2University of California, Irvine, Irvine, CA
Abstract Number: 1244
Presentation Title: Phosphatidylserine-targeting antibody reactivates tumor immunity and destroys tumor vasculature in mice
Presentation Time: Monday, Apr 08, 2013, 1:00 PM - 5:00 PM
Location: Hall A-C, Poster Section 5
Poster Board Number: 24
Author Block: Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe. UT Southwestern Medical Ctr., Dallas, TX
Abstract Number: 4326
Presentation Title: Phosphatidylserine-targeting ‘betabodies’ for the treatment of cancer
Presentation Time: Tuesday, Apr 09, 2013, 1:00 PM - 5:00 PM
Location: Hall A-C, Poster Section 36
Poster Board Number: 9
Author Block: Xianming Huang1, Dan Ye1, Troy Luster2, E. Sally Ward1, Philip Thorpe1. 1UT Southwestern Medical Ctr., Dallas, TX; 2Human Genome Science, Maryland, MD
In comparison with the Avastin + CP first-line trial there is another issue which I have brought up before,
but I think it is important so I am going to bring it up again. That is the total lack of a survival benefit
found in the Avastin trial for women. Now that lung cancer is the biggest cancer killer of women
this has even more relevance. Here are the numbers from the Sandler et al paper which reported
the Avastin trial results in the NEJM. The MOS overall was 10.3 months in the control arm,
and 12.3 months in the treatment arm.
For the Avastin + CP treatment arm
Male 210 patients (50%), Female 207 patients (50%)
CP control arm
Male 253 (58%), Female 180 (42%)
Subgroup Analysis
Hazard Ratio
Male 0.70, Female 0.98
Median survival control arm
Male 8.7 months, Female 13.1 months
Median survival Treatment arm
Male 11.7 months, Female 13.3 months
A sebsequent paper confirmed this lack of response in women. What is going on here is not clear.
Obviously the MOS for women increased the overall MOS for the trial. Why both the control and
treatment arms for women had a larger MOS, but not different, is the question. It will be very interesting
to see the breakdown for the bavi trial.
Good, yet another reason to expect better. Looking at your first-line estimates given in
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=84415167
if we took Jan 6 as the date the MOS was reached, that would be exactly 16 months since the
enrollment closed. I just don't see how the MOS could be less than 17-18 months. This will be fantastic
if the control arm comes in with 9-11 months, as I expect it will.
There are several reasons.
1) The PS scores in the phase IIa trial were PS 0 = 4%, PS 1 = 96%. As we have seen the PS score is
a major cofactor for survival. Most first-line NSCLC trials I have looked at have nothing like that
distribution, which means a more "normal" PS distribution would increase the survival.
2) The amount of carboplatin and paclitaxel used in the phase IIa trial was less than used in
the current phase IIb trial. This too should increase survival by some smaller extent.
3) The trial design can also be a factor. The first trial had a two-stage design. I don't know to
what extent this may have impacted the survival, but it is possible that it did.
4) The first trial was a single-arm trial, so we don't know how it would compare with a control arm with a
similar patient population.
There may be other factors, but these are enough to make it reasonable to expect a longer MOS.
Mojojojo's estimate was a range from 17.1 to 18.7 months, even the low end here is very good if the
control arm is around the historic mean of 9.8 months. I would think anything >50% would be a home run.
I should add that the results of the second-line NSCLC trial showed a doubling of MOS (at least in my mind),
or 60% officially. That should be a better indicator than the pancreatic trial.
But he was the only one who claimed that the MOS had already been triggered. According to his timeline
that happened sometime between Oct 18 and Dec 12. If you took Oct 25 that was exactly 4 months after
the enrollment closed. So it would not be unreasonable to get 5.6 months as an estimate for the MOS.
Genentech's T-DM1 approved for HER2+ breast cancer.
http://www.nytimes.com/2013/02/23/business/fda-approves-breast-cancer-drug.html?ref=health
Somehow I missed this. One of Genentech's top scientists has left for the UC San Diego School of Medicine as of Dec 1, 2012.
http://pathology.ucsd.edu/faculty/ferrara.htm
Napoleone "Napo" Ferrara is joining UC San Diego after working for 24 years at Genentech, where his research earned him a Lasker Award in 2010. The Lasker is nicknamed "America's Nobel" because it is so revered by medical researchers. Almost 80 scientists who've won a Lasker also have won the Nobel, including Shinya Yamanaka and John Gurdon, who were awarded the Nobel in physiology or medicine on Monday.
Ferrara is widely known for his work on angiogenesis, the formation of blood vessels that can feed tumors. His research contributed to the development of Avastin, one of the leading drugs used to fight breast, brain, colon and other forms of cancer. Ferrara also developed a treatment for wet, age-related macular degeneration, one of the main causes of vision loss in the elderly. The treatment can improve a person's sight and prevent a further loss of vision, says Genentech. The treatment has been used on more than a million people worldwide.
Dr. Ferrara also just won 3 million dollars:
http://www.nytimes.com/2013/02/20/science/new-3-million-prizes-awarded-to-11-in-life-sciences.html?ref=science
Bob, when Chris says
I agree with you here. From Mojojojo's analysis it would seem the first-line NSCLC MOS
occurred about 16 months after the end of enrollment (around early Jan 2013). That might
imply a MOS of about 18 months, but the minimum follow-up time after that before it is
reported might push the announcement out to May. That is why I think the inflection-point
date was changed from the first quarter of 2013 to the first-half of 2013.
There is no way anyone could calculate just how much error to introduce. They would have
no way of knowing how the trial would turn out, or how it was going at the time, or how the errors
would change the future behavior of the trial. What is interesting to me is that if a BP is behind
this then they must have really believed the trial would be a great success, or else why bother?
I would look at Mojojojo's estimate here. His range for the second-line of 10.5 to 11.5 months was the closest.
Note the final MOS was 11.7. For the first-line his range is 17.1 to 18.7 months, with a mean of 17.9 months.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=84415167
I am hoping for something interesting at the annual AACR meeting. Last year on March 1st Peregrine put out
a PR about the abstracts which were accepted for the meeting. The meeting is from April 6-10 in Washington DC.
Not much else on the horizon until we hear about the first-line NSCLC trial and ASCO. Good time to
take a break from all of this.
Sorry if I have contributed to your addiction!
The number in the PR, p=0.217, is based on the combined placebo and 1 mg arms from the trial,
even then it is a 60% increase in MOS. My number of 109% increase is the 3mg arm vs the
original control arm with MOS = 5.6 months. The original p-value for the 3mg arm vs placebo was 0.07.
You are confusing the increase in the MOS (number of months) with the statistical significance
of that increase. There was a large increase in the number of months of survival, but it wasn't
statistically significant. I wouldn't worry about it.
The MOS and overall survival here are the same. The fact that the result is not statistically significant
has been talked about endlessly and I have nothing to add. If this had been a phase 3 trial then it would
matter, but the results are excellent at this stage of the process.
All the N numbers are in these tables.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=84074948
Phase III Study of Second-Line Chemotherapy for Advanced Non–Small-Cell Lung Cancer With Weekly Compared With 3-Weekly Docetaxel
http://jco.ascopubs.org/content/23/33/8389.full.pdf+html
The standard treatment is 75 mg/m^2 of docetaxel every 3 weeks.
Thanks Wildhorses, I am not discouraged. I am going to take advantage of this
situation and buy a little more tomorrow.
Why is there this lack of reaction to great news? I think most investors are sheep who
can't see the forest for the trees. They can't think for themselves and are waiting for a
BP to show them the way.
No, I don't. I think we now see that with bavi + chemo the important result is the extension of overall survival.
I talked about that in this post
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=84668967
I expect the results for the first-line NSCLC trial to be at least as good as these.
I have no question that bavi works and this will be confirmed in phase 3 trials.
Mojojojo, looks like your estimate of 10.8 months was the best out there. I think the HR of 0.73 is very good too.
A 60% increase in second-line NSCLC blows away all other results from the past. I consider this a doubling
of MOS since the original control arm MOS of 5.6 is what I am comparing this with, in that case we have a 109% increase.
Yes, just like you, nobody really knows. It is all educated guess work.
I suspect that this is the same question as why can't we just drop the patients who got
the incorrect dosage from whatever arm they were in (placebo or 1 mg). I still feel the
reason this hasn't been mentioned by Peregrine is that there were too many patients who
got one incorrect dose, so the number of remaining patients would be too small. However,
I also still feel that one incorrect dose in many patients would have a very small effect on
the outcome of the control arm. There is another aspect to this too. It could be that
dropping patients could result in very unbalanced arms as far as patient characteristics go.
Hopefully when the data comes out this will be made clear.
Sure, the comparison won't be as good, but it still might be good enough.
The design of the trial was to have a 1:1:1 distribution of N among the three arms, so talk about a
possible disadvantage of this fact at this time is really not relevant.
The size of the trial (N), and how it is distributed between the arms of the trial, is one of the most basic,
and important, parameters of a trial. In all of the trials Peregrine has run N has been fairly small, with
all the arms having about 40 or less patients. If N was not important then why didn't they save their
money and just make all the trials half as large?
That is incorrect. If you look at the inclusion criteria from the archived ClinicalTrials.gov changes you
will see that from the beginning they allowed patients with PS <= 2. It must have been for one of the NSCLC trials.
The fact that patients with a PS score of 2 were included in the Peregrine pancreatic cancer trial is not unusual.
Perhaps it is not a good thing as far as trial results go since patients with a PS score of 2 don't live very long, but
in 10 of the 13 phase III trials in my table of pancreatic trials these patients were included.
Another chance at pancreatic cancer? I am thinking that a trial with bavi + abraxane + gemcitabine vs.
abraxane + gemcitabine could be interesting. Have to wait until abraxane + gem is approved. Then do a
phase II trial with the two arms. The idea is that the abraxane + gem keeps the patients alive long enough
for bavi to start showing an effect. Might be a couple of years though before this could happen.
Thanks. Read it on-line. Interesting.