Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘imatinib’

After a long lull on the targeted therapies front – outside of EGFR T790M in lung cancer – this year’s ASCO has plenty to be cheerful about with new data across multiple tumour types.  We can’t cover them all here, but more will be discussed in the Daily Live Blogs starting on Saturday.

Which drugs are going to be in roaring back after a quiet period?  Which ones will be having a more muted meeting?

ASCO16 Chicago 4For those of you who are working in the targeting therapy world, take heart, there is a future beyond cancer immunotherapy; it is not the universal panacea and will likely not cure every cancer, at least for now.

There’s still a market opportunity for targeted therapies in cancer, and as we mentioned in yesterday’s ASCO Preview, there is also potential for the combination of targeted therapies with immunotherapies, so long as the combined toxicity is manageable and doesn’t outweigh the benefits.

In this post we’re looking at a selection of targeted therapies in a variety of tumour types. There’s a lot to choose from at ASCO this year.

Here’s a few we think are worth highlighting upfront.

Subscribers can log-in to learn more or you can click on the Blue Box below to sign-up and become a member of the burgeoning BSB Community who appreciate the value of education, information and, even occasionally, infotainment…

Sarcoma is something we call one disease but actually represents 50-70 different histologies, which poses challenges for drug development.  Not only do you have to identify what’s the unique target, but it’s hard to accrue patients into trials, when a major center may only see a few of each sub-type.

Soft tissue sarcoma is an area of unmet medical need, and one I have been interested in since launching Gleevec in GIST (way back when) when I was fortunate to get to know many of the leading sarcoma experts.

Dr George Demetri

George D. Demetri, MD. Photo Credit: DFCI

One of these is Dr George Demetri, who is Director, Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School.

At the recent European Cancer Congress in Vienna, I had the privilege to talk with Dr Demetri about some of the latest research in soft tissue sarcoma.

We spoke about cancer immunotherapy, new small molecules and monoclonal antibodies, and the potential of targeting the epigenetic machinery.

A lot of what Dr Demetri is doing is currently “under the radar” and while he didn’t give any secrets away, he did give some sense of where some breakthroughs may occur in the not too distant future.  He also talked about how sarcomas with a specific target can be used for proof of concept clinical trials of novel agents.

Given the pressure that many companies are under to speed up their path to market strategies, accelerated approval in a rare tumour subset is one approach that can be considered.

It’s an exciting time in the field with the potential for several agents in development to move the needle and make a difference. I hope you enjoy this post, it was a real pleasure to talk with Dr Demetri again.

Subscribers can login below to read our interview with Dr Demetri at ECCO in Vienna.

One of the enduring legacies from the development of imatinib (Gleevec®/Glivec®) for the treatment of chronic myeloid leukemia (CML) is the long-term survival data from the IRIS (International Randomized Interferon versus STI571) trial that enrolled 1106 patients between June 2000 and January 2001.

Hagop Kantarjian M.D. presented on CML treatment choices at the 2012 Chemotherapy Foundation Symposium in New YorkHagop Kantarjian, M.D. Professor and Chair, Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston told the 2012 Chemotherapy Foundation Symposium (also known as the Greenspan Meeting in honor of the late Ezra Greenspan, M.D.) that:

the 10 year survival rate is 85% in patients treated with imatinib, and that this rises to 90% if you exclude deaths not related to CML.

No second-generation tyrosine kinase inhibitor (e.g. nilotinib, dasatinib, bosutinib) has yet to show a superior long-term survival benefit to imatinib. Dr Kantarjian noted that “whatever comes as a new treatment in the frontline therapy has to be able to beat that time, of a 10 year survival, if there is a big cost difference.”

The IRIS trial survival data for imatinib remains the gold standard by which other tyrosine kinase inhibitors will be judged.

In other words, notwithstanding the myriad of published CML data that shows second generation TKIs offer a deeper or more rapid molecular response, there’s still no data that shows you will actually live longer if you take any of them instead of imatinib.

That’s not to say there are no benefits to the newer second generation TKIs.

The patient advocacy session at the recent 16th Congress of the European Hematology Association in London focused on adherence to cancer treatments, and was filled to capacity, with the many attendees having to watch it from an overflow area.

Dr David Marin, Reader in Onco-Haematology at Imperial College, London presented research published last year in the Journal of Clinical Oncology that dramatically demonstrated how adherence to chronic myeloid leukemia (CML) therapy is the critical factor for achieving molecular responses.

In a study of 87 CML patients taking imatinib (Glivec®/Gleevec®) for a median period of 91 days, Dr Marin showed that no major molecular response (MMR) was observed when adherence was ≤ 80% and no complete molecular responses (CMR) were observed when adherence was ≤ 90%.  The graphical figure that he presented from his paper, dramatically shows how missing only a few doses of drug can have a major impact on outcome:

Source: Marin D, et al.  J Clin Oncol 2010; 28(14):2381-2388

Although the work by Marin and colleagues at the Hammersmith Hospital was undertaken with CML patients taking imatinib, the paper notes that adherence problems

“may apply equally to patients receiving second-generation tyrosine kinase inhibitors.”

Imatinib is the only TKI approved in the UK, thus that’s the only one available for studies there to date.

What made this data so compelling was the study rationale that used an electronic pill container, the medical event monitoring system (MEMS™) from the Aardex Group. This product contains a microchip that records the date and time it is opened.

Dr Marin’s study showed that “lack of adherence is underestimated by conventional methods.”  Self-reporting of adherence and pill counts are inaccurate compared to electronic data capture using MEMS (study subjects were unaware of the micro-chip in the pill bottle).

When psychologists at the Hammersmith Hospital subsequently interviewed patients who missed doses of drug, they found intentional and non-intentional adherence reasons.

A few excepts of  patient quotes from Dr Marin’s presentation:

Intentional non-adherence:

“Oh I can’t be bothered tonight, it’s not going to kill me [to miss a dose]”

“I thought there was no way I was going [on holiday] and being tired.”

Unintentional non-adherence:

“And sometimes you just forget”

“[the pharmacy] had no medication for me, so I went for nearly a week with no medication.”

Other speakers in the excellent patient advocacy session chaired by Jana Pelouchová (European Cancer Patient Coalition, Czech Republic) and Jan Geissler (CML Advocates Network, Germany) included Giora Sharf (Israeli CML patient’s Organization and CML Advocates Network, Israel) and Professor Rudolf Schoberberger (Medical University of Vienna, Austria).

Professor Schoberberger focused on the impact of drug packaging on compliance, particularly in elderly patients, and presented compelling research on how “child-proof” equals “age-proof.”  Sally Church in her video blog from EHA also discusses the patient advocacy session and how pharma/biotech companies could improve drug packaging.

The issue of adherence is a personal choice that every patient taking a chronic therapy makes. However, as Sally notes on Pharma Strategy Blog more patient and physician education is needed so that patients know there may be dramatic consequences from missing only a few doses per month.

Not only may adherence have a major impact on patient outcome, but as one questioner from France pointed out at the end of the EHA patient advocacy session, “for a statistician it is a nightmare.” Poor adherence in clinical trials “means that the true effect of a drug is not well known. Efficacy may be under-estimated if adherence is low.”

More monitoring of adherence in clinical trials through the use of MEMS technology may, therefore, be necessary to ensure that clinical trial data shows the true efficacy and adverse event profile of a drug.

I hope that the European Hematology Association (EHA) will make a webcast of this informative patient advocacy session publicly available online as it raised issues of considerable importance to patients, physicians and biotech/pharma companies alike.

ResearchBlogging.orgMarin, D., Bazeos, A., Mahon, F., Eliasson, L., Milojkovic, D., Bua, M., Apperley, J., Szydlo, R., Desai, R., Kozlowski, K., Paliompeis, C., Latham, V., Foroni, L., Molimard, M., Reid, A., Rezvani, K., de Lavallade, H., Guallar, C., Goldman, J., & Khorashad, J. (2010). Adherence Is the Critical Factor for Achieving Molecular Responses in Patients With Chronic Myeloid Leukemia Who Achieve Complete Cytogenetic Responses on Imatinib Journal of Clinical Oncology, 28 (14), 2381-2388 DOI: 10.1200/JCO.2009.26.3087

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European Hematology Association (EHA) Congress London 2011At the 16th Congress of the European Hematology Association (EHA) that was held in London this past weekend, the educational sessions were extremely well attended.

The reason for this was the quality of the thought leaders who presented on science and emerging treatments.

The quality of the education sessions and the fact they are repeated twice, so you can avoid schedule clashes, is one of the things I particularly like about both the American Society of Hematology (ASH) and European Hematology Association (EHA) annual meetings.

As I have written before while at EAU in Vienna, I’m not a fan of promotional satellite symposia.  As an example on the Thursday before EHA, attendees interested in CML could attend the Novartis symposia in the morning about how nilotinib was better than imatinib, then in the afternoon attend the BMS sponsored symposia to hear how dasatinib was also better than imatinib.  Indeed, two of the speakers were identical in both symposia, but with entirely different messages.

Two other satellite symposia also had speakers talking about second-generation tyrosine kinase inhibitors.  What, of course, was on everyone’s mind was when to use one second-generation TKI over the other?  Also given that imatinib is reimbursed in many countries, while nilotinib and dasatinib are often not yet available in that setting, the issue of how to treat patients second-line with these therapies was also a hot topic.

However, just attending the individual company-sponsored symposia, to me, meant that it was hard to put together a big picture of exactly what to do when.  Perhaps a better way to handle it would have been to have one CML satellite symposia sponsored by all the companies with a dog in the race (Novartis, BMS, Ariad, Pfizer). We might have heard what the experts really thought that way. 🙂

The other issue that arose during the meeting is how data is presented when looking strategically at one treatment or trial to another in the same indication.  Are you truly comparing apples with oranges?

M Baccarani European Hematology Association Congress London 2011As Professor Michele Baccarani pointed out, there is a big difference between data that shows a cytogenetic or molecular response “BY” a certain time as compared to “AT” a certain time.

“BY” can include patients who had a response then went in remission, so could present a higher number than “AT” data that shows only those patients who have a response at that cut-off date.  This is an important distinction, for example, when comparing data from the BMS DASISION trial and Novartis ENESTnd trials to long-term survival data for imatinib versus interferon-alpha from the IRIS trial.

So, it was left to the EHA education symposia to provide some practical guidance.  In an excellent presentation, Hagop Kantarjian M.D. from MD Anderson provocatively presented his CML treatment guidelines, and discussed when you would use one drug over the other along with the importance of routine monitoring to evaluate how well a patient was doing on therapy.

Webcasts from the EHA education sessions will be available online soon and are well worth watching if you were unable to be in London this past weekend.


I recently attended the annual meeting of the American Society of Hematology (ASH) in Orlando so thought I would share my general impressions (in no particular order):

Convention Center Food was Poor:

The food at the Orange County Convention Center reminded me of an airport – desperate choices, poor quality and overpriced.  As for no Starbucks or decent coffee shop, civilization has yet to reach Orlando! The Peabody hotel across the road had coffee shops that offered a $3 single espresso shot, but they ran out of pods on the Monday morning – faced with the overwhelming demand that seems to have not been anticipated!  Memo to Starbucks – look into a convention center franchise.

Cramming all the science in one day doesn’t work:

People go to a meeting such as ASH for many reasons – networking, business development, education, investigator meetings, but in the end, it is a scientific meeting.  The meeting ran from Saturday to Tuesday, yet nearly all the oral scientific program (biology and therapy) was crammed into one day of simultaneous sessions on the Monday – tough if you wanted to cover a product or pathway that targeted multiple therapeutic areas, many of which ran at the same time.

The Poster hall was like a graveyard:

You can tell I didn’t think this was a great meeting. Every time I went into the aircraft like hangar where the posters were housed, I ended up chilled to the bone. It certainly didn’t encourage spending much time there, and I was disappointed that a surprisingly high number of presenters did not attend the poster presentation receptions, when they were supposed to be available to answer questions.  Nobody seemed to check if anybody showed up, to me the whole point of a poster is being able to discuss it.

Why not publish the slides from the oral science presentations?

ASH, unlike ASCO does not make the slides of oral scientific presentations available online, so if you didn’t make notes, or break the rules (and risk being ejected) by taking an illegal picture on your phone or camera, then you missed it.  Abstracts are often submitted months in advance before the final data is analyzed, so by not making the slides available after the meeting, science to me is being hampered especially given the overlap of sessions on the Monday.  If an abstract is presented and published, the scientific information should be available to be shared. Isn’t that what science is about?  ASCO have it right, their virtual meeting program is outstanding.

Hospitality lives on – but only if you are an international doctor:

US doctors attending their annual meeting, are warned not to accept a free cup of coffee at an exhibitor booth if their state or employer prohibits the acceptance of such “gifts”, while foreign physician attendees are wined and dined.  You see signs for hospitality centers for European doctors or desks in hotels for company sponsored groups of foreign doctors – hard to believe there’s ethically not something wrong with these double standards.

A lack of quality educational materials:

While the free pen and notepad have long since gone the way of the dinosaur, this year there was noticeably fewer educational material to take away.  The debate as to whether doctors should pay for their own CME continues, but I do think many in the industry miss the opportunity by not providing educational material on the science, pathways and mechanism of action of new products.

The “Super Friday” is still alive:

Multiple industry sponsored satellite symposia (AKA “Super Friday” sessions) took place before ASH, with several at the Peabody Hotel. I have to say the food at the one I attended on personalized medicine was excellent, one of my best meals in Orlando.  They are not cheap to run: not only do 800-1000 people get fed, but a hotel room with audio-visual equipment has to be hired, a panel of experts are paid to talk about a topic, and many of the attendees come away with a glossy brochure.  Could this money be better spent elsewhere?  ASH has a large education component to it, and it was interesting to note that what the ASH education program committee chose as important topics to talk about and what the industry chose, were pretty different.  That is perhaps not surprising – after all if you choose the topic of the satellite symposia and it’s of relevance to your product, indirectly you are trying to influence prescribing behavior, otherwise why else would you fund it?  There is no such thing as a free lunch or dinner.

Multiple Myeloma was a hot topic:

There was a lot of interest in clinical trial results in MM.  The use of a maintenance therapy, and attempt to turn this into a chronic disease was a widely discussed topic, however many old drugs such as thalidomide have nasty side effect profiles such as peripheral neuropathy, while newer drugs such as lenalidomide are expensive but appear to only incrementally increase survival.  Results from multiple combinations of drugs and induction therapies were presented, I was left with the impression that although there is progress, there is still no major breakthrough in this disease area.

Nobody wants to talk about cost effectiveness:

The 800 lb gorilla in the room for hematology/oncology is the comparative effectiveness of one treatment versus another i.e. it’s cost/benefit, yet nobody wants to talk about it.  Take for example the treatment of CML, should you treat with imatinib (Gleevec) which has outstanding long-term survival data over several years thanks to the IRIS trial, or use a second-generation tyrosine kinase inhibitor (TKI) such as dasatinib or nilotinib that is around twice the price, more potent and slightly more effective but obviously we don’t yet know if it improves 5 or 10 year survival yet over imatinib.  Nobody wanted to talk about price – physicians currently live in an ivory tower.

If you are interested in information on what the hot scientific news was at ASH, then I encourage you to look at the excellent posts (here & here) published by my colleague on Pharma Strategy Blog.

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