Pancreatic Cancer | Pharma Strategy Blog

Nanoparticle drug delivery helps reduce tumour metastasis

By MaverickNY on August 23, 2010

Nanotechnology is a topic that fascinates me, ever since hearing some interesting data in pancreatic cancer at the American Association of Cancer Research (AACR) meeting last November on Molecular Targets in Boston.

Someone kindly sent me a paper from PNAS recently (link below), from 2008, which got my attention essentially because:

"Integrin aBv3 is found on a subset of tumor blood vessels where it is associated with angiogenesis and malignant tumor growth. We designed a targeted aBv3 nanoparticle (NP) encapsulating the cytotoxic drug doxorubicin (Dox) for targeted drug delivery to the expressing tumor vasculature."

Now, giving doxorubicin by the normal route of administration results in noticeable weight loss and other side effects when given systemically. Using nanotechnology, a 15-fold increase in anti-metastatic activity without concomitant weight loss, which is very interesting indeed.

The authors noted that integrin could represent an ideal vascular targeting receptor since it is highly expressed on the angiogenic endothelium and expression of this receptor on tumor vessels correlates with disease progression. This was first shown by Gasparini et al., in 1998 (see reference source below).

Meanwhile, in this 2008 study, the researchers used models from renal cell and pancreatic carcinoma to determine the effectiveness of the nanoparticle delivery system. Given that the results appear better with metastatic rather than primary tumour growth, I wondered if anyone was looking at this concept with currently approved drugs for metastatic disease?

A quick search for nanoparticle and cancer in the clinical trials database brought up mostly trials associated with nanoparticle paclitaxel (Abraxane) from Abraxis ($ABII). Of course, one of the challenges here is that in animal research, drugs and nanoparticles can be injected directly into the tumour thus avoiding systemic effects, whereas in human research, nanoparticle drugs are more typically combined with regular drugs and infused as normal.

It was, hover, no surprise to learn earlier this year that Abraxane is looking promising in 2nd line advanced pancreatic cancer as a single agent after failure of gemcitabine-based chemotherapy. At AACR last year, researchers from Mass General showed that Abraxane targets the tumour stroma, depleting it, thereby reducing the impediment to chemotherapy. The Nab-paclitaxel utilises endogenous albumin pathways via binding of the albumin to secreted proetin acid rich in cysteine or SPARC. Interestingly, pancreatic cancer is known to overexpress SPARC and therefore offers a logical target for the drug. Abraxis reported in May that the median overall survival was 7.3 months, which is impressive in a very hard to treat refractory population.

I wonder what the Nab paclitaxel data would look like in front-line treatment in combination with gemcitabine? Or what about using it in advanced renal cancer with any of the half dozen drugs already approved but with limited effectiveness? Would adding a nanoparticle delivery system such as Abraxane to the mix reduce metastasis, deplete the stroma and improve access to the tumour for the anti-angiogenic agents?

Overall, it's an interesting technology concept for improving drug delivery and we're still at relatively early stages of research. Hopefully, we'll hear more about nanotechnology and the broader application of new combination nanoparticles to cancer treatment in the near future. It takes significant investment, creativity in trial design and an intensive yet broad research program to drive results though. Celgene ($CELG) have since bought Abraxis and may be more willing to aggressively invest in the growth of this interesting drug.

I must say that the AACR Molecular Targets and Cancer Therapeutics meeting every November is one of my all time favourites, but it alternates with Europe every other year and will be in Berlin this November, so depending upon my schedule I may not be able to make it this time 🙁

Murphy, E., Majeti, B., Barnes, L., Makale, M., Weis, S., Lutu-Fuga, K., Wrasidlo, W., & Cheresh, D. (2008). From the Cover: Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis Proceedings of the National Academy of Sciences, 105 (27), 9343-9348 DOI: 10.1073/pnas.0803728105

Gasparini G, Brooks PC, Biganzoli E, Vermeulen PB, Bonoldi E, Dirix LY, Ranieri G, Miceli R, & Cheresh DA (1998). Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 4 (11), 2625-34 PMID: 9829725

Circulating IGF-I levels and pancreatic cancer risk

By MaverickNY on August 16, 2010

A couple of new papers will be reviewed this week, thanks to everyone who sent in links and suggested topics for discussion. I'll try and cover one a day, although there were so many worthy of consideration! Please do keep the ideas coming, they are much appreciated.

For today, here's one I came across last week in one of the American Association of Cancer Research (AACR) journals, Cancer epidemiology, biomarkers & prevention. The article discusses the evidence surrounding overexpression of insulin-like growth factor (IGF)-I and how that is implicated in human pancreatic tumours. To look at this concept further, the researchers decided to use longitudinal data from a study involving 187 cases and 374 controls, a not insignificant number as a starting point:

"We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk."

For those needing some background, I've covered the IGF pathway and some of the therapeutic inhibitors being developed in cancer before (see here, here, here and here for examples).

Michael Pollak, one of the authors from McGill University in Montreal, is a recognised authority on the subject and gave a fascinating talk on the science and biology behind the topic at the AACR Lung cancer meeting back in January this year. It's a particularly interesting pathway, not only because of the potential for cross-talk between pathways, but also feedback and feedforward loops, especially with the insulin receptor (IR), as Pollak elegantly illustrated.

It was therefore with great curiousity that I downloaded and read the paper (see the clickable journal link in the reference below), wondering what they found in the broader study. Essentially, they concluded that:

"A higher IGF-I/IGFBP-3 molar ratio represents increased free IGF-I, which may be a risk factor for pancreatic cancer."

Thus, rather than the absolute levels per se, the ratio may turn out to be a useful biomarker of the disease because the individual levels were not found to be helpful by the researchers, who:

"confirmed the nonsignificant associations for IGF-I, IGF-II, and IGFBP- 3 and risk of pancreatic cancer from previous studies."

As many of you know, pancreatic cancer is rather nasty, typically being diagnosed late because the symptoms can be subtle to detect and diffential diagnosis from other conditions associated with general malaise is hard. A new biomarker would be clearly be helpful, although the findings will need to be validated in future large scale longitudinal studies or from pooled analysis from other prospective trials.

Mind you, this research on pancreatic cancer reminded me of the phase I Merck study in the same tumour type, reported earlier this year, with a combination of different therapies including IGF-1R and EGFR inhibitors.

As far as I can remember, Merck also included the use of metformin in the protocol to manage hyperglycemia, which would also potentially block the IGF-1R – IR feedback loop seen in the figitumumab trial. Still, it would be interesting to know whether the IGF-I/IGFBP-3 molar ratio and free IGF were higher in the people with pancreatic cancer in that study.

Clearly, if IGF-I/IGFBP-3 turns out to be a valid biomarker of disease risk then it may be possible to identify, monitor and ultimately treat people with pancreatic cancer earlier, as well as develop better pipeline drugs, since we learn more about the biology of the disease in the process.

That can only be a great thing in the long run for improved outcomes.

Douglas JB, Silverman DT, Pollak MN, Tao Y, Soliman AS, & Stolzenberg-Solomon RZ (2010). Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 Molar Ratio and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology PMID: 20699371

Celgene buy Abraxis Bioscience for $2.9B

By MaverickNY on June 30, 2010

I did a double take at my inbox alerts this morning as things have been rather quiet of late in the Pharma and Biotech world. You can read the financial aspects of the deal in Celgene's press release.

While the timing might be a little bit of a surprise, the strategic acquisition is not and makes a lot of commercial sense for Celgene. There are a number of reasons for my thinking here:

It continues to build out of hematology with the beginnings of a solid tumour franchise since Abraxane is approved for breast cancer and has trials ongoing in pancreatic, lung, melanoma and bladder cancers.
The patent life for Abraxane is something like 2023, much longer than lenalidomide (Revlimid) and with few near term opportunities in the oncology pipeline, this adds extra protection.
Abraxane, while more expensive than generic paclitaxel, has probably been underfunded in clinical development and marketing efforts to date, so Celgene's thorough and aggressive approach may well kick start things, especially as they have cash to do so.
Buying Abraxis gives them access to nanotechnology, which I think will become more important in the future as an improved drug delivery system.

Late last year, while at the AACR Molecular Targets meeting in Boston, I wrote about nanoparticle technology and how it appears to offer a chance of improved outcomes in pancreatic cancer using Abraxane. The concept described by the researchers at Mass General was solid and promising, as was the early phase I data. Sometimes, it's not just about drug A being better or more potent than drug B, but the science and thinking behind solving a problem is elegant and well thought out. This was one of those cases. A couple of Phase II trials have so far yielded early but promising results in a devastating disease. The latest results, reported by the Abraxis in May this year, look encouraging so far.

Of course, most oncology specialists will know that melanoma, pancreatic and lung cancers as probably three of the four toughest cancers to get positive results in from phase III trials (the fourth is glioblastoma), but if any of them actually pan out with a significant difference in overall survival and FDA approval, then Celgene will have another winner on it's hands. I say 'if' because the road to approval and cancer drug development is littered with promising phase II studies that flopped or were sadly cancelled for futility in phase III.

Time will tell if this was a good acquisition or not, but for now, it's early but promising. That's ultimately both the lure and the heartache that is oncology.

You have to make the big plays to win.

The biology of pancreatic cancer

By MaverickNY on April 28, 2010

The cause of pancreatic cancer is still unknown, although there are risk factors involved, such as increased exposure to tobacco smoke and a family history of the disease. It is usually detected late when advanced stage disease has set in because most patients are asymptomatic for a long period and then it is too late. This raises the question of how can we learn and understand more about the biology of the disease as well as develop early warning signs via biomarkers used in screening?

It was therefore fascinating to be browsing through the latest edition of the New England Journal of Medicine over coffee this morning to discover an article on the medical progress in pancreatic cancer while simultaneously noticing an item on a new potential biomarker for the disease in Twitter! The NEJM review hasn’t been published online yet, so I’ll add the reference later.

Essentially, the NEJM article reviewed the biology of what we know of pancreatic cancer so far:

Results from successive accumulation of gene mutations (average of 23 per tumour)
Most patients with malignant disease carry 4 or more mutations (eg KRAS, CDKN2A, TP53, DPC4)
It’s extremely heterogeneous (more difficult to treat)
Formation of dense tumour stroma (dermoplastic reaction)
It is poorly vascularised (due to stellate cells and activation of TGFβ1, PDGF and FGFR)
Poor prognosis and treatment resistance has been conferred by the presence of cyclooxegenase-2 and PGFR, VEGF, SPARC and Hedgehog overexpression to name a few

The poor vascularisation of the tumour may well explain why anti-angiogenic therapies have not yielded promising results in the clinic to date.

Treating advanced cancer is always more difficult than earlier cancers in the neoadjuvant and adjuvant settings. The big challenge with pancreatic cancer to date, though, has been finding useful biomarkers for earlier detection, which would most likely impact outcomes for the disease. According to the NEJM article:

“The overall 5-year survival rate among patients with pancreatic cancer is <5%.”

That’s a pitiful number that needs to change.

There are a number of agents in the clinic for the treatment of advanced pancreatic cancer including inhibitors of SPARC, MEK, Mucin-1, IGF-1R, Hedgehog, PDGF and FGFR, Src, RAS, JAK-STAT and TNFα, for example.

Many of these agents are looking at single agent studies or in combination with the current standard of care, gemcitabine, itself with limited effectiveness. It is, therefore, quite hard to imagine that blocking one pathway alone is likely to be the panacea for such a hard to treat and highly complex cancer, as the graphic to the left shows (click to see the detail).

Source: Genway Bio

Meanwhile, progress may be possible on the detection front. Goicoechea et al. reported in PLoSONE that a type of protein called “palladin” is produced in large amounts in groups of cells in the stroma surrounding pancreatic tumours, known as the ‘tumour nest’. By measuring the levels of palladin in patient samples, doctors could have an improved way to screen for the disease, potentially detecting it earlier than current tests.

However, I say potentially, because these findings while interesting, need to be validated in large scale phase III clinical trials before we can really be certain of their long term validity. Nevertheless, it is a promising start for a devastating disease.

If there was one cancer that would hugely benefit from better earlier detection and diagnosis, it’s pancreatic cancer. We need more cowbell. That is all.

Update October 12, 2012

Another interesting paper on the biology of pancreatic cancer that is worth looking at if you are interested in this area is by Manuel Hidalgo and Daniel Van Hoff and was published earlier this year in the August 15, 2012 issue of the AACR journal Clinical Cancer Research.

Entitled, “Translational Therapeutic Opportunities in Ductal Adenocarcinoma of the Pancreas“, the full paper is currently available for free!

Goicoechea, S., Bednarski, B., Stack, C., Cowan, D., Volmar, K., Thorne, L., Cukierman, E., Rustgi, A., Brentnall, T., Hwang, R., McCulloch, C., Yeh, J., Bentrem, D., Hochwald, S., Hingorani, S., Kim, H., & Otey, C. (2010). Isoform-Specific Upregulation of Palladin in Human and Murine Pancreas Tumors PLoS ONE, 5 (4) DOI: 10.1371/journal.pone.0010347

#AACR10: The Kinase Dilemma

By MaverickNY on April 26, 2010

There are a lot of clinical trials out there right with tyrosine kinase inhibitors; unfortunately many will fail because they were rushed into phase II or III trials without thinking through all the options. There are, however, some smart companies out there who do think.

What was noticeable at AACR this year, was the surfeit of posters and presentations regarding logical combinations designed to eliminate escape routes and hence resistance. For example, cross-talk is a common problem between ligands, eg IGF-1R and EGFR, so combining the two may reduce the problem but that isn't the whole story.

Feedback loops also exist, so targeting PI3-kinase alone is less likely to be effective than targeting both PI3-kinase and mTOR. Neal Rosen from MSKCC showed some interesting data to this effect and argued cogently that oncogenes tend to lead to constitutive negative feedback. He also noted that the BRAF mutation predicts for sensitivity to MEKi, for example. Michael Korn also discussed the feedback activation loop between the RAS-ERK and PI3K pathways and how the inhibition of autophagy (where cells self digest themselves) can enhance apoptosis and the anti-tumour effect with smart combinations.

Targeting both MEK and AKT may therefore also have more effect than either alone, as you can see in the chart below:

Source: Array Biopharma

In a recent trial reported at the the ASCO GI meeting in January, Merck described an elegant design where IGF-1R, EGFR and AKT inhibitors were all combined to target advanced pancreatic cancer, with promising early results. I thought this was a prescient approach at the time, since it clearly sought to eliminate both cross-talk and feedback, so it was interesting to see numerous researchers advocating similar approaches in different tumour types based on the overexpression profiles at AACR last week. The design is based on rational biochemistry, which regular PSB readers will know I'm a big fan of, rather than randomly adding a kinase inhibitor to whatever is the standard chemotherapy of the day in a haphazard blunderbuss approach.

There are a number of MEKi and AKTi inhibitors out there (I counted nearly a dozen last time I checked), as well as a plethora of PI3-kinase and mTOR inhibitors, either alone or in combination. Merck and AstraZeneca announced an interesting deal earlier this year to jointly pursue research with their AKT (MK-2206) and MEK (AZD6244) inhibitors. This collaboration makes a lot of sense biochemically. Novartis (a client) have one of a broadest kinase pipelines in the industry and just added to it prior to AACR in a deal with Array BioPharma to license their MEK inhibitors, of which ARRY-162 is the lead candidate.

The compounds that ultimately win the race may not necessarily be the ones furthest ahead in clinical trials right now, but the ones with the smartest clinical trial designs to eliminate some of the issues associated with kinase inhibition – cross-talk, feedback, feed-forward loops and additional mutations.

MEKi and AKTi are two of my favourite kinase approaches right now because they offer the flexibility to add to existing TKI's such as erlotinib, sorafenib or everolimus, for example, potentially improving the outcomes further in a variety of different cancers, never mind the future combination possibilities. It's going to be a very interesting and hot area to watch in the near future, that's for sure.

If you have any thoughts or questions on this fascinating topic, please do add them in the comments below.

4 Comments

Improved survival in a rare cancer with chemotherapy

By MaverickNY on April 8, 2010

An interesting article has been published in the latest New England journal describing how the addition of a cisplatin to gemcitabine improved survival by two months in biliary tract cancer. Currently, there is no standard treatment for this rare disease, so a solid phase III trial (ABC-02) represents an important step forward for treatment.

Biliary tract cancers are tumours that develop in the gallbladder and bile ducts. Those that develop in the bile duct within the liver are known as cholangiocarcinomas. Approx. 6500 new cases of gallbladder carcinoma are diagnosed each year in the US. Interestingly, chronic inflammation appears to be a common aetiologic factor in the disease development. There has been a rise in incidence of the cancer in recent years, which may possibly be attributable to the association between liver disease and increasing hepatitis C virus infections.

Although there are no standards, gemcitabine has been the bedrock of palliation therapy for the disease based on the experience in pancreatic cancer. The earlier ABC-01 phase II trial suggested a benefit in adding a platinum to gemcitabine.

In the current ABC-02 phase III trial, the median overall survival with the combination was 11.7 months and 8.1 months in the gemcitabine alone group, a significant improvement of 3.6 months.

As a result, the combination of cisplatin and gemcitabine is likely to become the new standard of care for the treatment of biliary tract cancer. As we learn more about the science and biology underlying the disease, further improvements may be possible with the addition of targeted agents.

Reference

Valle, J., Wasan, H., Palmer, D., Cunningham, D., Anthoney, A., Maraveyas, A., Madhusudan, S., Iveson, T., Hughes, S., Pereira, S., Roughton, M., Bridgewater, J., & , . (2010). Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract Cancer New England Journal of Medicine, 362 (14), 1273-1281 DOI: 10.1056/NEJMoa0908721

West, J., Wood, H., Logan, R., Quinn, M., & Aithal, G. (2006). Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001 British Journal of Cancer, 94 (11), 1751-1758 DOI: 10.1038/sj.bjc.6603127

El-Serag HB, Engels EA, Landgren O, Chiao E, Henderson L, Amaratunge HC, & Giordano TP (2009). Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans. Hepatology (Baltimore, Md.), 49 (1), 116-23 PMID: 19085911

2 Comments

Genvec's TNFerade fails in phase III trials for pancreatic cancer

By MaverickNY on March 31, 2010

It's been a busy week on the road here at Icarus and today and tomorrow are no exception, so finding time to blog is a little more challenging.

Yesterday, I got back from a biomarker symposium in Princeton to find that my Twitter and almost everything else Pharma related were full of Genvec's announcement that their phase III trial for TNFerade was being discontinued in pancreatic cancer.

It's not really a drug, more an experimental gene therapy, that according to Genvec:

"Acts as an adenovector, or DNA carrier, which contains the gene for tumour necrosis factor-alpha (TNFα), an immune system protein. It is directly injected into the tumour. After administration, TNFerade stimulates the production of TNFα in the tumour."

The abandonment of the trial isn't really big news though, as the drug previously failed in melanoma and other cancers, despite the magic words, "promising phase II data." Let's face it, pancreatic cancer is also probably one of the toughest nuts to crack out there in the oncology world. Sadly, it was doomed to failure from the beginning; I would have been more surprised had it actually worked.

Genvec have a raft of other trials that are either currently enrolling people with various cancers or have recently finished enrollment; I wonder what the fate of the overall program will be given the repeated negative results?

At the beginning of this month many pharma and biotech pundits smiled at the 'beware the Ides of March' quips on Twitter, but by the end of March they seem much more accurate than one may realise!

Looking back through the months posts, there were several spectacular phase III flops from Pfizer and Roche, Roche's ocrelizumab and AstraZeneca's cediranib bit the dust, the ODAC meeting on 22nd was brutal for Cell Therapeutics and ChemGenex with neither getting approved, Antisoma's ASA404 crashed on Monday, Merck KGaA are reviewing the EU cardiac data for Erbitux, which may also have implications for BMS and ImClone in the US. Yikes, I could go on…

Let's hope that April and May bring more positive news to talk about.

3 Comments

The Biotech IPO isn't dead yet!

By MaverickNY on February 8, 2010

Recently, I noticed that oncology companies are in the news for raising new financing or even announcing IPO's, and wondered if that was an anomaly after the credit shutdown following the Wall St crisis. In general, my perception was that they seemed to be down overall. To find out more, I checked out the VC funding statistics at OnBioVC:

Surprisingly, oncology dominates the market at the moment, with the latest data being available from 3Q09: nearly one-third were from oncology alone during that period. According to the report, they represented:

"… a diverse therapeutic approach; from small molecules targeting the inhibition of receptor tyrosine kinase to HDAC to metallo-enzymes to PI3K and mTOR, as well as a variety of mAb’s and therapeutic vaccines."

In more terms, though, the aggregated dollars raised per sector is significantly down over the same period in 2008:

But overall, the total number of financings for Biotech are up, thanks to a strong growth in the medical device sector, although the biopharma sector is down slightly:

Last October, Auxilium received proceeds, net of offering expenses and underwriting discounts and commissions, of approximately $115.7 million. The company closed its previously announced public offering of 3,000,000 shares of common stock at a price of $34.50 per share.

Meanwhile, last week was a busy one.

Firstly, Ironwood raised $188M from their IPO in one of the biggest deals of the decade (more than Eyetech's $150M in 2004) by selling over 16M of shares at a price of $11.25. It was, however, perceived to be a discount price, because their SEC filings in November hoped for a higher target of $14-16/share. As a friend commented last week, "Well, $188M isn't chump change!"

Secondly, Reuters reported that the private French Biotech company, AB Science,

"is preparing for a 50 million euro ($70 million) initial public offering next month in a move that could make it France's first biotech stock exchange listing since mid-2008."

What's interesting about AB Science is that the company have yet to officially announce or confirm the date of the IPO, although they made clear their intent to pursue one in 1Q10 when we interviewed Alain Moussy, the CEO, in October.

The company has an interesting KIT inhibitor on the market in Europe, masitinib, for mastocytosis in dogs and is now developing the drug in pancreatic cancer for humans. In order to fund the phase III trials, more financing is needed so the IPO is clearly a sign that the company is going places.

This week heralds the annual BIO CEO meeting in New York, where there will doubt be a lot of interesting discussions and presentations going on. The schedule is packed with a quite a few oncology focused companies, so more news will be covered on this blog later this week as details emerge. Sadly, I will miss the event, as I'll be at the ePharma meeting in Philadelphia. More on that tomorrow!

5 Comments

Cross-talk: what it is and how it impacts cancer research

By MaverickNY on January 27, 2010

A Pharma friend who regularly reads this blog attended the ASCO GI meeting last weekend and phoned me to say that cancer is indeed getting much more complex. She was also highly amused at the buzzword bingo post from the AACR Molecular Targets meeting:

"Well, I just thought you might like to know that the latest buzzword bingo is 'cross-talk'"

Funnily enough, I was writing a report on cross-talk at the very moment she called. Cross-talk occurs when two powerful signaling pathways interact, leading to interactive processes between them downstream of the original receptors.

Another Pharma buddy sent me the slides from a presentation on the Merck IGF-1R inhibitor, MK-0646, phase I results of which were reported in pancreatic cancer. One of the focus of the presentation was 'cross-talk' according to the abstract:

"Receptor cross-talk between IGF-1R and EGFR and enhanced IGF-1R-induced activation of the PI3-kinase/Akt pathways mediate resistance to anti-EGFR agents such as erlotinib. IGF-1R + EGFR antagonists result in synergistic antitumor activity in preclinical pancreatic cancer models."

When you actually look at the pathways involved, you can see that things are indeed very complex and cross-talk is not surprising, as Pollak et al., showed in 2004:

This means that inhibiting the IGF-1R pathway alone with a inhibitor such as Pfizer's figitumumab or Merck's MK-0646 is unlikely to be effective because cross-talk between the receptor and AKT/mTOR or MEK pathways may well have an impact and lead to an escape route for the cancer cells to continue surviving. For this reason, we can see that the recent futility reported in the figitumumab lung cancer trial is not completely surprising. However, combining the drug with an AKT or MEK inhibitor may well yield better results.

In the Merck study, the majority of patients had an objective response or stable disease when the IGF-1R inhibitor was combined with erlotinib, an EGFR inhibitor. Cross-talk between IGF-1R and EGFR has been shown in preclinical models of pancreatic cancer.

These early results are promising for the compound, but much work is still needed to determine suitable predictive biomarkers and ideal combinations/sequencing before moving forward into a phase III trial.

Pollak, M., Schernhammer, E., & Hankinson, S. (2004). Insulin-like growth factors and neoplasia Nature Reviews Cancer, 4 (7), 505-518 DOI: 10.1038/nrc1387

3 Comments

Science and medical conferences – is there value in going?

By MaverickNY 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.

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.

Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts from the ‘Pancreatic Cancer’ category