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Posts tagged ‘ASCO’

The big day for ASCO 2010 abstracts

By on May 20, 2010

Tonight at 6pm, the ASCO abstracts of live online with the exception of the plenaries, late breakers and clinical review abstracts, which will published at the meeting.  7 policy exceptions were granted under SEC guidelines, meaning that limited information to be made publicly available in advance of the meeting:

Abstract 8010: Lenalidomide maintenance after transplantation for myeloma. 

Abstract LBA4007: The AVAGAST trial: A randomized, double-blind, placebo-controlled, multicenter phase III study of capecitabine and cisplatin plus bevacizumab or placebo as first-line therapy in patients with advanced gastric cancer. 

Abstract LBA4507: Denosumab versus zoledronic acid for treatment of bone metastases in patients with castration-resistant prostate cancer. 

Abstract LBA1: Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. 

Abstract LBA4511: A randomized, double-blind, placebo controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castrate-resistant prostate cancer (metCRPC): Survival results of CALGB 90401. 

Abstract LBA7502: Results from ARQ 197-209: a global randomized placebo-controlled phase 2 clinical trial of erlotinib plus ARQ 197 versus erlotinib plus placebo in previously treated EGPR-inhibitor naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). 

Abstract LBA8512: A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma.

Of these 7, no doubt keen investors will be interested in the first ($CELG) and last ($DCTH), and analysts will be anxious to see the denosumab data ($AMGN), but the ones that I will be most interested in are ARQ197 ($ARQL) and bevacizumab (Avastin) ($RHHYG).  We already know that the Avastin data was negative in gastric and prostate cancers, but positive in ovarian cancer from Roche's previous press announcements.  Ovarian cancer badly needs new options that improve outcomes for women suffering with the disease.

Sometimes though, the best data is not always in the plenary session, witness the Herceptin trial in adjuvant HER2+ breast cancer a few years ago when everyone stood up in a packed session and clapped because the data was simply stunning and groundbreaking. 

Tonight's peek at the available abstracts should give us some clues about what might be interesting. I'll try and schedule some quick posts this evening as I'll be out at client meetings all day tomorrow, great timing, not.

The interesting dichotomy of oncology research vs clinical medicine

By on May 18, 2010

Over the past few years it has been interesting to watch AACR organise and group it's sessions by pathways, so you end up with a higgledy piggledy collection of different inhibitors, therapeutics, chemotherapies etc as well as a mix of different tumour types.  This works well for the scientist, less so for the clinician who may specialise in only a few cancer types.  

Meanwhile, at ASCO, everything is organised by cancer track, so if you want to search for data on say, MEK, AKT or c-MET inhibitors for example, then the data is now all over the place and trying to get round and find it all is much more difficult.  The chances of missing something, or worse, having clashes in interesting sessions is much higher.  I'm already looking a potential schedule with too many clashes and periods of nothing.  That's not a very efficient way to organise the data, yet this was not something I experienced at AACR to the same extent.

image from farm4.static.flickr.comPersonally, I find myself much preferring the AACR approach because it's ultimately logical and allows you to see patterns and trends more strategically, providing you approach it sensibly. You do need to think in 3D though, much like that 3 level chess board beloved by Spock in the original Star Trek. This way allows you to see potential connections and future approaches more easily rather than being hemmed in by tumour siloes.

In the long run, I confidently predict that the future trend of personalised medicine is going to be more based on a pathways approach allied with mutational analysis based on constitutive activation, rather than simply thinking in terms of cancer type by line of therapy.  Once you start understanding which subsets exist and which inhibitors can be combined together, it is not hard to see a new world evolving out there that may lead to better outcomes and improved quality of life.

Who knows, we might even be able to get rid of toxic chemotherapies altogether and prescribe a cocktail of more targeted agents based on the patients characteristics.

Now that would be a fine thing indeed.  Thoughts?

Photo Credit: GiftsforyouBiz

ASCO 2010 Preview #1

By on May 11, 2010

It's only 3 weeks to go to the Annual ASCO meeting in Chicago so I thought it would be a good time to kick off the annual preview of key data.  One of the things that sets the tone of the meeting is which abstracts are in the plenary session.  Sometimes I don't attend the session if it looks arcane, but this year looks really interesting and worthwhile attending.

The selected abstracts comprise the following:

#LBA1: Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or Fallopian tube cancer (FTC): A Gynecologic Oncology Group study.

#2: Weekly paclitaxel combined with monthly carboplatin versus single-agent therapy in patients age 70 to 89: IFCT-0501 randomized phase III study in advanced non-small cell lung cancer (NSCLC).

#3: Clinical activity of the oral ALK inhibitor, PF-02341066, in ALK-positive patients with non-small cell lung cancer (NSCLC).

#4: A phase III, randomized, double-blind, multicenter study comparing monotherapy with ipilimumab or gp100 peptide vaccine and the combination in patients with previously treated, unresectable stage III or IV melanoma.

Now, three of these trials promise some excitement.  The one I'm surprised about is the French Intergroup study looking at a taxane plus platinum in lung cancer.  In case anyone is wondering, the trial (link) states that:

"It thus seemed to us justified to compare a standard arm, the vinorelbine or the gemcitabine (with the choice of the center) in monotherapy with an experimental arm, association carboplatine + paclitaxel."

Carboplatin plus paclitaxel (with or without bevacizumab) is pretty much standard as first-line treatment for non-small cell lung cancer (NSCLC), so now we know that the doublet is likely more effective than single agent gemcitabine or navelbine in the elderly too, but for me all four are old drugs, likely available as generics and it's all an iteration of what we mostly know already.  I'm particularly interested in new and exciting agents that are coming through or new indications or more recent drugs as we see them expand their utility.

The results are no doubt important, but plenary important?  It could
have well led off an oral lung cancer session and received attention at
Best of ASCO perhaps, but for me, the plenary sessions should be
about groundbreaking new therapies or indications, which the other three
clearly are.

Still, the Korean study in ALK-positive people with NSCLC really gets my attention because we've only heard about a US study in the past, so seeing how this evolves Globally is vitally important.  Pfizer have done a nice job speeding this agent, PF-02341066 (crizotinib), through development having recognised the significance of the rearrangements and then invested significant resources to moving it forward.  They should be commended for that and I sincerely hope the results continue to be positive. 

What is also nice is that I've come across a few new ALK inhibitors at AACR and elsewhere that may work in patients where crivotinib stopped working, perhaps as a reult of new mutations.  This is an exciting area of research, even if it just affects a small subset of patients.  Cancer is a heterogeneous disease so researching and identifying different subtypes that can be then targeted with new therapeutics is critical.

After excitedly listening to the BMS R&D Day, I was expecting that ipilimumab might have a chance of a plenary with the melanoma data because the example they gave just took your breath away – this is what we all live for in cancer research – something that really makes a difference to the disease and makes you go, "oh wow!"  You can read more about that commentary here.  Roche and Plexxikon also have a promising compound in development (PLX4032) that targets BRAF.  At Roche's R&D Day, they noted that they planned to present the phase II data later this year at a melanoma meeting.  That's how the timing rolls sometimes.

The bevacizumab (Avastin) data in ovarian cancer was previously announced by Roche earlier this year to be positive, so this is excellent news for women with ovarian cancer.  I really look forward to seeing the results in full.  What's particularly important about this trial is that it is the first positive phase III study of an anti-angiogenic therapy in advanced ovarian cancer.  I think Judah Folkman would be mightily pleased with the progress of angiogenesis inhibitors such as Avastin so far, if he could see them.  It's all too easy to forget the visionaries in research and focus on the results.

For some reason, ovarian cancer always seems to be the poor cousin to breast and lung cancers and regimens that work in either tend to dribble down to ovarian cancer years later, but all three share many similar regimens.

From tomorrow, I'll start an ASCO series taking a look at some of the bionic biotechs with interesting data and a review of some of the big cancers and the potentially interesting data that may be worth highlighting and checking out.

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ASCO 2010

By on May 7, 2010

To answer all the emails and requests I've been getting for the pre-ASCO blogs: the series is rolling out next week with a different topic each day for consideration. 

This week has been a tad busy with various client projects, so I'll have time over the weekend to finish the ASCO research and analysis.  I will also provide some links to other commentators posts I've come across as well for extra delectation and mind broadening :-).

I'll be doing a 3 week road trip from AUA in San Francisco to ASCO in Chicago to EHA in Barcelona, so will cover AUA and EHA at the meetings.

Happy Friday, everyone!

#ASCO10

By on April 30, 2010

I've been getting a lot of enquiries lately about what I think will be interesting at ASCO this year, so next week will see a couple of posts on this topic after some research has been completed with the crystal ball this weekend.

The American Society of Clinical Oncology (ASCO) will be in Chicago rather than Orlando in June for the next 10 years and have announced that this year's hashtag is #ASCO10.  You can follow all the chatter around the topic on Twitter for the next 2 months, no doubt.  

AACR_SM

It will be interesting to see what they are doing with social media after the success their cousins at the American Association of Cancer Research (AACR) have been having, particularly with the warmth with which they (AACR) have encouraged and embraced science bloggers and Tweeters.

What I liked about AACR's approach is that they did a great job sharing and rolling out the science for those who were following via podcasts and webcasts both on their site and also in iTunes. When EU presenters were unable to attend key presentations due to the Volcano, they didn't miss a beat and improvised with teleconferences to live slides.  Great job!

In comparison, I confess that I was a little disappointed to see ASCO are charging $100 a pop for podcasts and $75 for the virtual meeting with no audio. Clearly a much more commercial organisation.

Still, it's usually an interesting meeting packed with data and a great opportunity to see what's coming through in early phase I trials from preclinical research.

In the meantime, if you have any specific requests, please add them to the comments below and I'll do my best to include them in the pre-meeting analysis.

Watch this space!

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Ipilimumab from BMS looks like an interesting new melanoma drug

By on March 5, 2010

It's been a frantic week on the work front and today was no different, but I wanted to highlight a really interesting slide from the BMS pipeline presentation yesterday afternoon.

Here's one of the slides Elliot Sigal, President of R&D, showed from one of the ipilimumab trials.  More data may be available at ASCO if the submitted abstract is accepted, but for now, even though it's only an n of 1, a picture tells a thousand words:

Picture 29
Source: BMS

After all the recent good news about malignant melanoma, hopefully at least one of these promising agents will make it to market in the not too distant future, offering people suffering with the condition a glimmer of hope.  I sincerely hope the CTLA4 results turn out to be durable.

In the meantime, we can all wonder until June, when the annual ASCO meeting will held.

 

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Erbitux improves survival in patients with metastatic colorectal cancer and wild type KRAS tumours

By on January 25, 2010

The American Society of Clinical Oncology (ASCO) held their annual symposium on Gastrointestinal cancers over the weekend in Fort Lauderdale, FL.  I was unable to attend the meeting, but it was interesting to follow it remotely via various people at the event. 

In 2008, van Cutsem first presented the interim phase III data from the front line trial of cetuximab
(Erbitux) with FOLFIRI in metastatic colorectal cancer (mCRC) in a plenary session at the ASCO annual meeting.  The data demonstrated that biomarker data suggested that the presence of wild type rather than mutant type KRAS predicted response to cetuximab in mCRC.

The updated CRYSTAL data was
probably the most anticipated abstract at this meeting.  Here's a snapshot from the abstract:

Picture 200The data above clearly shows a superior response rate, progression-free survival (PFS) and overall survival (OS) in favour of cetuximab in wild type KRAS.

What was also interesting is that BRAF, another mutation that has been shown to increase resistance to EGFR inhibitors, was not predictive of cetuximab activity, based on pooled data from the CRYSTAL and OPUS trials presented by Prof Kohne.

Overall, these data indicate that testing for KRAS mutational status is a valid way of deciding which patients should receive EGFR inhibitors such as cetuximab for the treatment of metastatic colorectal cancer.  Patients with mutant KRAS or BRAF mutations are less likely to do well on such therapy.

It will be interesting to see whether future trials with a RAS/RAF inhibitor such as sorafenib (Nexavar) with cetuximab are being considered in combination to overcome resistance.

{Updated: I should clarify that the wt KRAS effect is an EGFR class effect as you can see from similar data on panitumumab (Vectibix) in the second line setting in this abstract. 

The presenter, Peeters, noted that in patients with wild type KRAS:

  • PFS was 5.9 months for panitumumab plus FOLFIRI
    vs. 3.9 months for FOLFIRI alone (HR=0.73). 
  • Median OS was
    14.5 months for the study arm vs. 12.5 months for FOLFIRI alone
    (HR=0.85). 
  • Response rate for the panitumumab arm was
    35% compared with 10% for patients assigned to FOLFIRI alone. 

As with cetuximab, there was no difference in PFS, OS or
response rate in patients with mutant KRAS tumours.  The study met its primary endpoint, so it will be interesting to see if regulatory approval will be forthcoming in the second line setting for panitumumab.}

Acknowledgement:  Many thanks to Kerri Wachter who was at the meeting and provided information and tips that lead to this post.

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Science and medical conferences – is there value in going?

By on January 24, 2010

One of the great things about travelling to scientific conferences around the world, is catching up with old friends, meeting new people, learning new things and also seeing some wonderful sights when least expected.

IMG_6038 Here's a quick shot I took at dusk on my 3G iPhone took walking from
the bus stop to the hotel I was staying in for the recent AACR meeting
on molecular origins in lung cancer. 

It was nice to get out at the end
of the day for some fresh air, but the sunset was certainly an added bonus and a heartening welcome after the chill of the East coast winter!

Some meetings you can get a decent flavour of what's going on from the press releases and reports coming out from good science writers, reporters and analysts such as Brooke Wang, Kerri Wachter, Mike Huckman and Roxanne Nelson.  You can't attend every conference, but you can trust in a few good men (and women) to tell the stories in a straightforward and accurate way.

After a while, I can tell who is actually reporting live from the meeting and who is just rehashing a press release or media briefing – the quality of the reporting and analysis shines through beyond mere data repetition :>}.

One of the biggest things I personally gain from being on the spot is the chance to interact with key opinion leaders and ask them questions.  Of course, you can do this by email or phone too, assuming you can track them down in a timely fashion, but checking the nuances on the spot is extremely valuable both for greater understanding and immediacy.

Right now, I'm following the ASCO Gastrointestinal Cancer Symposium from Fort Lauderdale on Twitter via the #GICaSymp hashtag.  Kerri is tweeting and reporting from there and several Pharma buddies are also attending and sending updates by email.  I'm particularly keen to hear what Dr Eric van Cutsem has to say in his update about KRAS and biomarkers from the CRYSTAL trial in colorectal cancer.

#ASCO Early detection of pancreatic cancer using PAM4 as a biomarker

By on January 22, 2010

"Researchers have developed a novel immunoassay for detecting early-stage pancreatic cancer that identifies and quantifies blood levels of the PAM4 protein – a unique antigen present in almost 90 percent of pancreatic cancers and precancers."

ASCO GI Cancer Symposium, 2010

Wow, that little snippet from the ASCO press releases from the Gastrointestinal symposium in Florida woke me up while sipping coffee this morning!

The reason is that pancreatic cancer is an insidious disease and most patients are diagnosed late, usually in stage IV when there is little that can be done to successfully attentuate the cancer.  For years, researchers have struggled with ways of detecting the cancer earlier when treatments are more likely to be effective without confusing cancer from pancreatitis.

Approximately 7% of pancreatic cancer cases are detected at an
early stage, before the cancer has spread to other parts of the body. 
The survival rate for early stage pancreatic cancer is around 20%, compared with just 1.8% for those diagnosed when the disease has metastasized.

The PAM4 antibody, also called clivatuzumab, from Immunomedics ($IMMU) used in the assay reacts with a protein produced by pancreatic cancer cells.  It appears that the protein is not detectable in normal pancreatic cells and is rarely detected in pancreatitis (inflammation of the pancreas), making it potentially highly specific for pancreatic cancer.

The researchers evaluated an immunoassay for the PAM4 protein in 68 patients who had pancreatic cancer surgery and 19 healthy controls.  They found that the test was 62% sensitive for detecting stage 1 pancreatic cancer (disease confined to the pancreas), 86% sensitive for stage 2 disease (disease which has spread to nearby organs) and 91% sensitive for stage 3/4 cancers (local and distant spread).  Overall, the assay was 81% sensitive for detecting all stages of pancreatic cancer; while not perfect, it would represent an enormous improvement on current detection rates.

The obvious next step is to validate the test on a larger scale with more patients to determine if it has utility as a diagnostic tool to detect people at risk for pancreatic cancer such as patients with a history of tobacco use, or those with genetic or other medical factors on a yearly basis, to enhance the chance of early detection.

The investigators also suggested that the clivatuzumab antibody may also prove useful for treating the disease by acting as a carrier for agents (such as radioactive isotopes labelled with Y90) that can target and kill cancer cells, but this idea is pure supposition at present and as yet, unproven.  Immunonomedics have a phase I trial ongoing with clivatuzumab in pancreatic cancer

At the ASCO GI symposium there was, however, some interesting new data in the treatment of pancreatic cancer as Pfizer announced the final results from a randomized Phase III
trial of sunitinib (Sutent) in patients with advanced pancreatic
neuroendocrine tumors, a type of cancer which originates in the
hormone-producing area of the pancreas. 

Sunitinib appeared to more than double the
time the patients with lived without
disease progression compared with patients treated with placebo; results showed that median progression-free survival (PFS) was 11.4
months in patients treated with sunitinib compared with 5.5 months in
patients treated in the placebo arm.  Overall survival was also prolonged. 
Adverse events were similar to those observed in other sunitinib
studies.

The sunitinib results are particularly interesting, not only because they improve survival beyond the six months typically seen with the disease, but also because other VEGF inhibitors such as bevacizumab (Avastin) previously did not appear to be effective in slowing the disease.  Sunitinib, though, is a multi-kinase inhibitor that also targets other pathways other than VEGF, including c-KIT, PDGF, FLT3 and RET, suggesting that dual inhibition of perhaps VEGF and PDGF is necessary in this disease.

On the basis of these results, Pfizer filed supplemental applications
for approval in pancreatic neuroendocrine tumours with the US, EU and
Canadian authorities, so help for patients may well be coming sooner than expected.

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Shifting gears: another year in Pharma and Biotech

By on January 4, 2010

As the New Year begins and everyone shifts gears after the two week break over the Holidays, I realised a few things that were relevant to me personally.  This year will mark my 7th seventh year in consulting, six of those running Icarus.  Is it really that long?  Wow.

Over time, this has become a blessing because while consultants come and go ‘in between jobs’, we’re still here providing longevity and reassurance that a relationship is there for the long haul and not as flash in the pan merchants.

That’s a good thing and a bad thing though.  Those that stand still will not grow but be left behind.  You have to keep innovating and creating to survive in this world.  Reliability is also important, but delivering value and intelligent insight and analysis rather than mere data is what most of our customers seem to want and need.

The other day, someone asked me why we read a lot of scientific papers as well as going to so many conference and meetings.  The answer is that’s how we stay ahead of current and future trends, new ideas and innovation.  It’s a lot of data to shift through but then, that’s what clients want: more than they understand themselves, as no one wants to hear what they already know back.

Still, I have a long list of lot’s of interesting concepts and ideas to discuss on this blog in 2010, some new, some reinvention of old ideas in different guises, some yet to reveal their true results (from phase III studies) at conferences such as AACR, ASCO and ASH.  It will be fascinating to see what new technologies and pipeline drugs emerge as real new advances in their area.  Somehow, the New Year also brings a renewed sense of urgency and hope quite unlike any other month in the year.

Last week, I was browsing through company pipelines and was struck at how little is ready for market this year, with many phase III projects probably not maturing until 2011.  2010 may well be the year of consolidation in Pharma and Biotech, where many companies take stock and get ready for a big push in 2011, when the biggest patent expiries are most likely to hit. There’s a few expected this year too, though, as Pharma Gossip nicely highlighted this morning.

January promises to be a busy start to the year:

  1. It heralds many companies presenting year end reviews and their forward look at 2010.  I’ll be keeping an eye on these and observing any new trends as they come out.  
  2. The AACR-IASLC joint conference on Lung Cancer is also being held later this month from 11-14th Jan in San Diego (details here and here), so if anyone wants to meet up for networking then, let me know.  There’s a lot on pathways, stem cells, genome-wide approaches, as well as models for earlier detection, so it should be a very interesting meeting.

In the meantime, we also have a stack of client reports due, proposals to write, phone calls and email enquiries to return etc… sound familiar?  

Ok, let’s roll!  

Welcome back everyone, a wonderful New Year to y’all.

PS 

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