Gone for good.
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If you take the PFS and MOS results from the bavi + docetaxel MBC trial, to get
MOS/PFS = 20.7/7.4 = 2.8. Apply that to the bavi + docetaxel second-line NSCLC
trial to get estimated MOS, at a minimum,
1 mg/kg: 4.2 * 2.8 = 11.8
3 mg/kg: 4.5 * 2.8 = 12.6
average = 12.2 months, more than double control arm MOS, and counting.
Yes, and being not anywhere near must mean some number like only 40% of the treatment arm patients have died?
It certainly doesn't sound like it is within a few percentage points of the MOS event does it?
Thanks.
So what is your estimate of when the control MOS event occurred?
I am confused because I am thinking about the case of the control arm MOS being as short as 5.5 months.
Since there are six 3-week treatment cycles = 4.1 months, it seems to me possible that the control MOS
could have been reached before the last patient enrolled even finished his/her treatment,
which is the Feb 11th date I believe.
Mojojojo, I am still not sure how "triggered" is defined. It may not be defined as 50% + 1. Even though the MOS
is 50% alive/dead, the "trigger" for announcing the result could be something else, like 75% dead.
This would be different from the percentage needed to estimate the statistical significance.
In today's webcast King indicated one of the ways in which the new imaging agent, now in a phase I trial,
could be used is to find chemo agents that work better than others at increasing the amount of PS exposed.
As I said in my posts # 82577, 82585 I think the new trial with Xeloda, radiation, and Bavi could be really good.
Roche might be interested in that one since they sell Xeloda.
You have a point. An exclusive deal for bavi in NSCLC using taxotere, both first and second-line in Europe,
or ex-USA, is what SA would want I imagine. Who needs a patent on the combo then? Peregrine's patents might
actually cover the combination of bavi + docetaxel.
Might just happen, although it is possible that the bavi + CP first-line NSCLC phase II trial will be better!
Wildhorses, welcome to the party, see my posts # 82111, 82113.
Can they get a new patent for using the combination of taxotere and bavi?
I am so glad to be wrong! I think RRdog is closest to the final results for MOS. Hot dog! (goes with Holy Cow!).
Can't wait to get data from pancreatic and liver cancer trials in the next few months.
Thanks, I use Chrome usually, but I could see the slides.
There is this conference, but today is the last day to submit a late-breaking abstract, so maybe they got one in on-time.
2012 Chicago Multidisciplinary Symposium in Thoracic Oncology
Chicago Marriott Downtown Magnificent Mile in Chicago, September 6-8, 2012
The 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology will offer valuable information on the multidisciplinary treatment approach for thoracic malignancies. This multidisciplinary meeting will promote interaction between the surgery, medical oncology and radiation oncology disciplines to achieve the best possible outcome for thoracic cancer patients. The meeting will also bring together physician specialists from around the world for interdisciplinary discussions on the latest research and state-of-the-art care for thoracic cancers.
http://thoracicsymposium.org/
Geez, I haven't heard the webcast yet, it wouldn't work for me. It sounds fantastic!
There is clinical support for a second-line NSCLC control MOS much less than 6 months. In the paper by Ciuleanu et al, 2012.
Efficacy and safety of erlotinib versus chemotherapy in
second-line treatment of patients with advanced,
non-small-cell lung cancer with poor prognosis (TITAN):
a randomised multicentre, open-label, phase 3 study.
www.thelancet.com/oncology Vol 13 March 2012
Background Erlotinib, docetaxel, and pemetrexed are approved for the second-line treatment of non-small-cell lung
cancer (NSCLC), but no head-to-head data from large clinical trials are available. We undertook the Tarceva In
Treatment of Advanced NSCLC (TITAN) study to assess the efficacy and tolerability of second-line erlotinib versus
chemotherapy in patients with refractory NSCLC.
Findings Between April 10, 2006, and Feb 24, 2010, 2590 chemotherapy-naive patients were treated with first-line
platinum doublet chemotherapy, of whom 424 had disease progression and were enrolled into TITAN. 203 patients
were randomly assigned to receive erlotinib and 221 were assigned to receive chemotherapy. Median follow-up was
27·9 months (IQR 11·0–36·0) in the erlotinib group and 24·8 months (12·1–41·6) in the chemotherapy group. Median
overall survival was 5·3 months (95% CI 4·0–6·0) with erlotinib and 5·5 months (4·4–7·1) with chemotherapy (hazard
ratio [HR] 0·96, 95% CI 0·78–1·19; log-rank p=0·73). The adverse-event profile of each group was in line with previous
studies. Rash (98/196 [50%] in the erlotinib group vs 10/213 [5%] in the chemotherapy group for all grades; nine [5%] vs
none for grade 3 or 4) and diarrhoea (36 [18%] vs four [2%] for all grades; fi ve [3%] vs none for grade 3 or 4) were the most
common treatment-related adverse events with erlotinib, whereas alopecia (none vs 23 [11%] for all grades; none vs one
[<1%] for grade 3/4) was the most common treatment-related adverse event with chemotherapy.
Interpretation No significant differences in efficacy were noted between patients treated with erlotinib and those
treated with docetaxel or pemetrexed. Since the toxicity profiles of erlotinib and chemotherapy differ, second-line
treatment decisions should take into account patient preference and specific toxicity risk profiles.
From the slides it is obvious they are pushing the effect of bavi + docetaxel. They show results from the
MBC trial and preclinical data. So, as of the May 21 announcement a majority ( > 50%) of the patients were
alive on the treatment arms. That does tell us the MOS had not been triggered by then and presumably
have not yet been triggered.
Thorpe is one of the invited speakers at the Annual Antibody Engineering and Antibody Therapeutics Meeting
IBC’s 23rd Annual Antibody Engineering and 10th Annual Antibody Therapeutics International Conferences:
December 2-6, 2012, San Diego, CA USA.
http://www.ibclifesciences.com/antibodyeng/overview.xml
RRdog, I am very much looking forward to how this plays out.
Last month there were two papers in the NEJM about the antibodies
against PD-1 and PD-L1. There were a lot of articles written about it.
See my posts # 80964, 80971, 80981, 82402. I think that bavituximab
will be shown to be far superior to the two antibodies in the NEJM papers.
This appeared yesterday and also goes on about the same antibodies.
From the July 10, 2012 issue of Cancer Cell
The Future of Cancer Treatment: Will It Include Immunotherapy?
Jeffrey A. Bluestone1,2,* and Eric J. Small2
1Diabetes Center
2Department of Medicine
University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143, USA
......
In summary, these two studies provide
compelling evidence that immunotherapy
is no longer the future of cancer
treatment, but is very much a current
reality. The articles by Brahmer et al.
(2012) and Topalian et al. (2012) provide
critical insights into how further understanding
of the basis of cancer immunology will lead to
advances that benefit our patients
I expect that you are correct and they will tell us that one or both of the MOS events
has not triggered yet. I think it should be close to 12 months by next week.
I want to believe!
Maybe they just don't follow PPHM as closely as we do and so aren't really that aware
of what is happening (or not). Of course they may not believe that anything good will
happen either and so don't pay much attention. I don't really care about them.
We are all in the dark to some extent. My estimate for when the MOS would be announced
will be past by the end of this week. The quarterly conference call will be next Monday
so maybe news then. Hopefully no news is good news.
To me that means the MOS has not been reached, but will be reported when it does happen.
The phase II prostate trial. I hadn't noticed before that only patients previously treated with docetaxel are being recruited.
Not sure if the idea is that this is an advantage for treating with bavituximab, or not. From ClinicalTrials.gov:
"This is a Phase Ib/ IIa study to evaluate the use of Cabazitaxel plus Bavituximab as second-line chemotherapy in patients who have a histological diagnosis of adenocarcinoma of the prostate. This study will enroll patients with CRPC, who have been previously
treated with docetaxel or a docetaxel-containing regimen. "
So, putting the pieces together. I see these two new phase I trials leading to a phase II trial which combines
the use of bavituximab, Xeloda, and radiotherapy in LARC, along with imaging using I-124-PGN650 to
monitor the treatment before surgery to remove any remaining tumor, and maybe after surgery as well to
detect any recurrence.
One more example showing another use.
Role of FDG-PET Staging in Selecting the Optimum Patient for Hepatic
Resection of Metastatic Colorectal Cancer
STEVEN M. STRASBERG, MD 1* AND FARROKH DEHDASHTI, MD 2
1Section of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO
2Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO
http://onlinelibrary.wiley.com/doi/10.1002/jso.21729/abstract;jsessionid=1FD450A3679FB18C165D6A179B27AF0C.d02t03
Some quotes...
The outcome of treatment of colorectal liver metastases has
improved substantially as a result of advancements in surgery,
chemotherapy, and imaging. The use of positron emission tomography
(PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) to study intrahepatic
and extrahepatic spread of colorectal cancer has significantly
contributed to the management of this disease. FDG-PET is currently
used for diagnosis, staging, restaging, and in the follow-up of patients
with colorectal cancer. FDG-PET can be used for monitoring the effect
of chemotherapy and radiotherapy. Primarily through its ability to
detect extrahepatic metastases, it has reduced nontherapeutic laparotomies
and, to a lesser extent, futile liver resections. FDG-PET also has
been used to predict outcome.
....
Also chemotherapy reduces FDG accumulation in malignant lesions,
presumably due to downregulation of hexokinase activity [2], so that
less FDG is accumulated, potentially resulting in nondetection of
viable tumors.
---------------------------------------------------------------------------------------------
So maybe I-124-PGN650 could be an improvement in this case.
As a follow up of this thesis here are two recent publications co-authored by the PI of the I-124-PGN650 imaging trial,
Farrokh Dehdashti, MD. The first combines PET/CT and LARC.
Positron Emission Tomography with [(18)F]-3'-Deoxy-3'fluorothymidine (FLT) as a Predictor of Outcome in Patients with Locally Advanced Resectable Rectal Cancer: a Pilot Study.
Dehdashti F, Grigsby PW, Myerson RJ, Nalbantoglu I, Ma C, Siegel BA.
Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA, dehdashtif@mir.wustl.edu.
http://www.springerlink.com/content/p2582005x3890244/
Combined PET/CT image characteristics for radiotherapy tumor response in lung cancer
Manushka Vaidya a, Kimberly M. Creach a, Jennifer Frye a, Farrokh Dehdashti a, Jeffrey D. Bradley a, Issam El Naqa a, b,
a Washington University, Saint Louis, MO, USA
b McGill University, Montreal, QC, Canada
http://www.sciencedirect.com/science/article/pii/S0167814011006268
At least we could get a PR announcing the two new phase I trials, that is news isn't it?
Having these two new phase I trials appear at the same time may not be coincidence. The
trial of bavituximab plus radiotherapy and Xeloda I think could be intended for pre-surgery in LARC.
So, I-124-PGN650 could be used to follow the treatment and assess the tumor size before surgery to
guide the removal of the remaining tumor. In the I-124-G250 trial in my last post that is what they did
with renal cell cancer, but their antibody is specific for renal cancer cells.
This is the phase I trial for I-124-G250
Preoperative characterisation of clear-cell renal carcinoma
using iodine-124-labelled antibody chimeric G250 (124I-cG250)
and PET in patients with renal masses: a phase I trial
http://oncology.thelancet.com Vol 8 April 2007
Summary
Background Preoperative identification of tumour type could have important implications for the choice of treatment
for renal cancers. Antibody cG250 reacts against carbonic anhydrase-IX, which is over-expressed in clear-cell renal
carcinomas. We aimed to assess whether iodine-124-labelled antibody chimeric G250 (124I-cG250) PET predicts clearcell
renal carcinoma, the most common and aggressive renal tumour.
Methods 26 patients with renal masses who were scheduled to undergo surgical resection by laparotomy received a
single intravenous infusion of 185 MBq/10 mg of 124I-cG250 over 20 min in this open-label pilot study. Surgery was
scheduled 1 week after 124I-cG250 infusion. PET and CT scanning of the abdomen, including the kidneys, within 3 h
before surgery was planned for all patients. The obtained images were graded as positive (defined as a tumour-to-healthy-
kidney ratio >3 to 1) or negative for antibody uptake, and the surgeon was informed of the scan results before
surgery. After surgery, resected tumours were histopathologically classified as clear-cell renal carcinoma or otherwise.
The trial is registered on the clinical trials site of the National Cancer Institute website http://clinicaltrials.gov/ct/
show/NCT00199888.
Findings One patient received inactive antibody and was excluded from analysis. 15 of 16 clear-cell carcinomas were
identified accurately by antibody PET, and all nine non-clear-cell renal masses were negative for the tracer. The
sensitivity of 124I-cG250 PET for clear-cell kidney carcinoma in this trial was 94% (95% CI 70–100%); the negative
predictive value was 90% (55–100%), and specifi city and positive predictive accuracy were both 100% (66–100% and
78–100%, respectively).
Interpretation PET with 124I-cG250 can identify accurately clear-cell renal carcinoma; a negative scan is highly predictive
of a less aggressive phenotype. Stratification of patients with renal masses by 124I-cG250 PET can identify aggressive
tumours and help decide treatment.
Mojojojo, I had two posts about the antibody G650 before, see # 78086, # 78087
This new phase I trial for rectal adenocarcinoma resembles a phase II trial which also
used capecitabine and radiation, but Avastin was added. Note that capecitabine is a
prodrug which converts into 5-FU internally and is made by Roche and sold as Xeloda.
This paper about the trial is freely available. It gives some background on the treatment
of LARC (locally advanced rectal carcinoma).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179720/?tool=pubmed
Great to finally see a phase I study combining radiotherapy with bavituximab, and
also the imaging trial.
http://www.clinicaltrials.gov/ct2/show/NCT01634685?term=bavituximab+OR+Peregrine&recr=Open&rank=2
http://www.clinicaltrials.gov/ct2/show/NCT01632696?term=bavituximab+OR+Peregrine&recr=Open&rank=6
Yes, I was wondering about the denominator. To me it is clear that it is greater than
5 and less than 6. Looking at all the control arms for second-line NSCLC I would say
closer to 6 than 5, say 5.6-5.9 months. Will be interesting to see how much difference
there is between the 1 mg/kg and 3 mg/kg arms.
I would be thrilled. The treatment of cancer will be changed in a major way. Hopefully a lot more research
money will go into immunotherapy. Peregrine would be able to pick and choose from offers made by
big pharma for a piece of the action. Would help to fund my retirement too.
How about a betting pool for the bavi (3mg/kg) + docetaxel MOS result with a jug of your moonshine as the prize?
I don't follow that logic? But, yes it is a blockbuster.
Mojojojo, thanks for the update. I can see how the enrollment problems would push the time forward
for MOS triggering. However, the conclusion that the attorney hire and recent share price activity is an
indicator of the treatment arms being triggered is stretching it. It could also be due to just anticipation that
MOS will be very good based on the time now past the May 21st announcement. All I can say is we will
just have to wait and see. Even if your estimate of 10.3 months is correct it will be very good. Do you
think the control MOS could be much less than 6 months?
Radiation and bavi works really well in the mice/rat models used in pre-clinical work. The problem will
be in trying this with humans. Radiation isn't usually used with metastatic cancer. I believe it is mostly
used after surgery in advanced cancers that are still localized. So it would make most sense to try
adding bavi to radiotherapy in stage III NSCLC after surgery. The idea here would be that adding bavi
would reduce the incidence of recurrent cancer, or stop it altogether.
Yes, I agree. I think the strategy is to use bavi with the SOC to show how addition of bavi to SOC can
increase survival without a lot of added side effects. That makes approval of bavi by the FDA, and
adoption of bavi by oncologists, all the easier.