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

Posts tagged ‘Prostate Cancer News’

American Urological Association 2012 Annual MeetingAlthough there is a lot of buzz around ASCO 2012 in a few weeks time, this weekend sees the start of the annual meeting of the American Urological Association (AUA) in Atlanta.  AUA 2012 runs from May 19-23 at the Georgia World Congress Center.

A few of the sessions that caught my attention include:

  • Basic Science Symposium on Nanomedicine and its application to urology. Several speakers will discuss how nanoparticles can be used for drug delivery, imaging and as therapeutic tools.
  • Society for Basic Urologic Research (SBUR) and Society of Urologic Oncology (SUO) joint meeting on personalized medicine and novel targets for cancer therapy.

For those of you who missed AUA 2011, you can obtain a flavor of the meeting from Sally Church’s video that was published on Pharma Strategy Blog.

If you can’t be in Atlanta, you can follow updates from the conference on Twitter (hashtag #UR012). A few people to follow at the meeting include @cooperberg_ucsf, @daviesbj, @MaverickNY@NeuroUroGastro.

We are aggregating the #URO12 tweets so you can easily catch up on the conversation and news below:

View-of-Paris-from-European-Association-of-Urology-2012-CongressToday sees the start of the 27th annual European Association of Urology (EAU) Congress at the Palais des Congrès in Paris.

The meeting runs from 24-28 February, 2012. Over 10,000 delegates are expected, and more than 1193 abstracts have been accepted for poster and video sessions.

In addition to a scientific programme, this meeting also has a strong educational component with numerous courses through the European School of Urology (ESU) and hands-on-training to improve surgical skills in cooperation with the EAU Section of Uro-Technology (ESUT), the EAU Section of Urolithiasis (EULIS) and the EAU Section of Robotic Urology (ERUS).

If you can’t be in Paris, then EAU have some live webcasts and they will be sharing a lot of the content from the meeting as well as undertaking video interviews.  Check out the EAU 2012 Paris Congress website for more information.

For those that are interested in following the twitter coverage of the meeting, the hashtag is #EAU12, and EAU is @uroweb on twitter.  You can also use the twitter aggregator below:


Prostate cancer is the second leading cause of cancer death in men, so it was good news this morning when Medivation & Astellas issued a press release that showed positive data from the phase 3 AFFIRM trial for MDV3100.

MDV3100 produced a 4.8-month advantage in median overall survival compared to placebo.

The estimated median survival for men treated with MDV3100 was 18.4 months compared with 13.6 months for men treated with placebo.

MDV3100 provided a 37 percent reduction in risk of death compared to placebo (Hazard Ratio=0.631).

To put the 4.8 month survival advantage in context, this compares favorably with 3.9 months for abiraterone (Hazard Ratio =0.646), in the COU-AA-301 trial.

Positive data was expected given the sound scientific rationale behind MDV3100 and the preliminary data (abstract 4501) presented at the ASCO annual meeting this year. J Clin Oncol 29: 2011 (suppl; abstr 4501).

The drug has a high affinity for the androgen receptor (AR) that is highly expressed on prostate cancer cells.  You can read an excellent interview on Pharma Strategy Blog with Charles Sawyers, who was one of the co-inventors.

MDV3011 blocks the androgen receptor (AR) from moving into the nucleus and activating growth genes and is a more complete inhibitor of AR than bicalutamide.

One hot topic of conversation at ASCO was the potential to combine MDV3100 (androgen receptor blocker) with abiraterone acetate (Zytiga) (androgen synthesis inhibitor), thereby shutting down upstream and downstream activity of the driving receptor in advanced prostate cancer.  The scientific rationale for this appears sound, so it is likely that a combination clinical trial may well be done to test this hypothesis at some point in the future.

MDV3100 has a significant advantage over abiraterone acetate (Zytiga) in that concomitant steroids are not required. Daily steroids have their side effects.  Urologists in particular will be attracted to MDV3100 and its ease of use.

Clinical trials in prostate cancer are ongoing with a multitude of new emerging therapies including TAK-700, Cabozantinib (XL184), radium-223 chloride (Alpharadin), BPX-101, Prostvac-VF, ipilumumab, Custirsen (OGX-011), dasatinib (Sprycel), lenalidomide (Revlimid) and ARN-509 to name but a few.

It is a therapeutic area with a lot going on after very little activity for a decade. The positive interim data for MDV3100 announced today is good news for prostate cancer patients, and we await presentation of the data next year.

Medivation and Astellas plan to hold a pre-NDA meeting with the U.S. Food and Drug Administration (FDA) in early 2012, so US approval could be possible later next year.

The phase 3 ALSYMPCA prostate cancer trial results for radium-223 chloride (Alpharadin) were presented at the recent ECCO ESMO ESTRO 2011 European Multidisciplinary Cancer Congress in Stockholm. This was the highlight of the meeting for me.

There was also exciting data in Breast Cancer (BOLERO-2) that you can read more about on Pharma Strategy Blog.

Alpharadin from Norwegian company, Algeta, is the first new treatment for advanced prostate cancer that not only prolongs overall survival (OS) but delays time to first skeletal related event (SRE) in metastatic castration resistant prostate cancer patients.

Leading physicians at the meeting believe that it will be “practice changing.

The Alpharadin data may also have an impact on other bone targeted agents in development for prostate cancer such as cabozantinib (XL184).

Sally Church, PhD (who writes the Pharma Strategy Blog) is quoted by “The Street” as saying that “Alpharadin raises the bar for Exelixis. They have to produce overall survival data now.” Overall Survival (OS) remains the primary regulatory endpoint in prostate cancer drug development.

Prostate cancer experts Johann de Bono and Cora Sternberg also mentioned, in presentations at the Stockholm meeting, that in the future it will be increasingly difficult to do placebo controlled trials in Prostate Cancer given the new treatment options available.

Alpharadin is not yet approved in Europe or the USA, but is on fast track for approval by the FDA in 2012.

Chris Parker (Royal Marsden Hospital) presented the Alpharadin ALSYMPCA trial data as a late breaking abstract in the presidential session at ECCO ESMO 2011. He also conducted a media briefing that I was fortunate to video.

You can watch this below. In it he explains how radium-223 choloride works and why he (and others) believe this may change the standard of care for prostate cancer patients with bone metastases. It is well worth watching!


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One piece of hot news at the 2011 European Multidisciplinary Cancer Congress (twitter #EMCC2011) taking place in Stockholm this weekend is the data on radium-223 chloride (Alpharadin) in metastatic castration resistant prostate cancer. The phase 3 ALSYMPCA trial results were presented in yesterday’s presidential symposia by Dr Chris Parker, Consultant Clinical Oncologist at The Royal Marsden Hospital.


The Scandinavian location for the presentation could not have been better, given that Alpharadin was developed by the Norwegian company Algeta. Bayer Schering Pharma AG have the worldwide commercial rights, but Algeta maintains a co-promotion option in the United States.

I first picked up on Alpharadin in a presentation given at the American Urological Association (AUA) annual meeting by Oliver Sartor (Tulane) earlier this year when he reviewed new prostate cancer products in development.

Algeta-Radium-223-Chloride-ASCO 2011-Abstract-4620At the ASCO 2011 meeting in Chicago there was a poster on the Alpharadin Phase 2 trial data (see the figure on the right) that caught my attention given that it showed an overall survival (OS) advantage.  This news was, however, largely drowned by the interest in cabozantinib (XL184).

The result is that Alpharadin has to many come out of left field. It is a promising compound for the treatment of prostate cancer that will provide new treatment options for patients with metastatic disease. In particular, use in combination with other therapies such as abiraterone acetate (Zytiga) may prolong survival to a greater extent than either does individually.

Currently, radium-223 chloride (Alpharadin) is only in investigational use and is not approved in Europe or the United States. It is, however, on the fast track towards FDA approval in 2012.

ALSYMPCA phase 3 prostate cancer data presentation ESMO ECCO 2011What makes Alpharadin exciting as a new treatment option for castration resistant prostate cancer (CRPC) is that the ALSYMPCA trial data shows that it not only provides a significant median overall survival (OS) benefit of 2.8 months compared to placebo (14 months versus 11.2 months, p=0.00185, HR 0.695), but significantly delays the time to first skeletal event by 5.2 months (13.6 months versus 8.4 months, p=0.00046, HR 0.610).

The overal survival (OS) benefit seen in the ALYSMPCA phase 3 trial is comparable to other approved agents in the post-docetaxel setting for CRPC. However, where it is unique is in the additional effect it has on skeletal related events (SRE), a common occurrence in metastatic prostate cancer.  Bone metastases are painful and have a significant impact on quality of life.

Other compounds that target the bone microenviroment such as denosumab (Xgeva), provide a delay in the time to first skeletal event in prostate cancer patients but to-date have not been shown to confer an overall survival advantage. This means that Alphardin is the first bone targeted agent to confer both an overall survival and a delay in time to first skeletal event.

After Dr Parker’s presentation of the ALSYMPCA phase 3 trial data yesterday here in Stockholm,  Professor Wim Oyen of the Department of Nuclear Medicine in Nijmegen discussed the data.

What he noted was the high tolerability of Ra-223 chloride (Alpharadin) as compared to other radiopharmaceuticals for treatment of patients with bone metastases.  He discussed how the emission of alpha particles allows for a short range effect (a few cell diameters) that is very localized, but with a large biological effect.

Oyen highlighted the “opportunity for improving patient outcome by adding Ra-223 in regimens of combination therapy,” something that Dr Parker speculated about in his media briefing.

Professor Oyen also saw “an opportunity for improving patient outcome by using Ra-223 in an adjuvant setting.”  His conclusion based on the phase 3 ALSYMPCA trial data presented was that radium-223 chloride (Alpharadin) is an “effective, very well tolerated and convenient treatment modality.


Dr Parker mentioned to me, while waiting for a train back to Stockholm, that the ALSYMPCA trial data he presented had not yet been submitted for publication. He said he would be disappointed if it did not appear in the New England Journal of Medicine. Given that it is groundbreaking and “practice changing,” I would be surprised if it is not published in the NEJM in due course.

I am sure that we will be hearing more about radium-223 chloride (Alpharadin) in the forthcoming months, especially now it is on fast track to FDA approval in 2012.

Although not a cure for prostate cancer, the ALSYMPCA trial data presented here in Stockholm is further good news for patients, and will provide a potential new treatment option for urologists and oncologists.

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Radium-223 (Alpharadin) will be “Practice Changing” is how Michael Baumann, President of the European CanCer Organisation (ECCO) and Jean-Charles Soria, Co-Scientific chair of the 2011 Stockholm Multidisciplinary Cancer Congress described the prostate cancer clinical trial data to be presented in the Presidential (plenary) session on Saturday September 24, 2011.

Alpharadin is the first bone targeted therapy to show an overall survival (OS) advantage in metastatic castration-resistant prostate cancer (mCRPC). To date, none of the other therapies targeting bone in prostate cancer such as zoledronic acid (Zometa), denosumab (Xgeva) or cabozantinib (XL184) have shown any overall survival benefit.

The Alphardin data from the phase 3 ALSYMPCA trial that will be presented in Stockholm shows an increase in overall survival of 2.8 months compared to placebo (median OS of 14 months with Alpharadin versus median OS of 11.2 months with placebo, p=0.00185, HR=0.695).

What is big news is that Alpharadin also significantly prolongs time to first skeletal related event (p=0.00046; HR=0.610). This is tremendous news for prostate cancer patients given the number that experience bone metastases.

It is not, however, good news for Amgen and denosumab (Xgeva). Amgen have tried to associate the improvement in symptoms and decline in skeletal related events with survival, but have failed to obtain any overall survival data (OS). This is something that Alphardin achieves as well as a significant reduction in time to first skeletal related event (SRE).

What Alpharadin has effectively shown is that by nuking bone metastases using a weak alpha emitting radium-223, overall survival (OS) can be prolonged in a way that targeting rank ligand does not. This is ground breaking news and the 2011 Stockholm Multidisciplinary Congress have rightly recognized the importance of this data with a plenary session. For further information on how Alpharadin works – see my previous blog post about the ASCO 2011 phase 2 data.

At the press briefing late friday afternoon in Stockholm, Dr Chris Parker of the Royal Marsden Hospital and PI of the ALSYMPCA study said that “Radium-223, a novel alpha-pharmaceutical, may provide a new standard of care for the treatment of  CRPC patients with bone metastases.”

There is no doubt in my mind that it will lead to a new standard of care. What’s more as Dr Parker speculated in the press briefing, there is no reason why Alphardin could not be combined with androgen receptor antagonists such as the recently approved abiraterone acetate (Zytiga).

Both are well tolerated and operate by different mechanisms of action.  It’s hard not to believe that the overall survival of CRPC patients will be increased by such a combination.

When approved, Alpharadin and any possible combination with Zytiga, may further delay the use of sanofi-aventis’ cabazitaxel (Jevtana) in the post-doctaxel CRPC setting. It may also potentially have an impact on the use of sipuleucel-T (Provenge) in the asymptomatic population.

The Alpharadin phase 3 trial results is exciting news from the 2011 Stockholm Multidisciplinary Cancer Congress. I will be writing more after Dr Parker presents the data in the Presidential session later today.

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As many of you know, I previously wrote up on this blog the results from the Prostate Cancer Intervention versus Observation trial (PIVOT) that were presented during the plenary session at the recent American Urological Association (AUA) 2011 annual meeting.

Other science bloggers who were at the meeting also wrote about the presentation (see Scott Hensley’s excellent post on NPR’s health blog).

In fact anyone in the press room at AUA (I had a media pass as a science blogger) could have reviewed a copy of Dr Wilt’s presentation immediately afterwards and written about it.

However, what surprises me is that the data from this trial, which to many was the highlight of the AUA meeting and may be practice changing for urologists, has had relatively little or no pick-up by the mainstream news media.  The only reason I can think for this is due to the fact there is no abstract available, press release or other information for the media to use as reference.  Why is this?

As a scientist it makes no sense to me to present the results of a landmark study in the plenary session of a major scientific congress and not to share the data, especially when the data could have a major impact for men diagnosed with early prostate cancer and the practice of evidence based medicine.  Are urologists seriously supposed to rely on the notes they made from a rushed presentation or blog posts to guide them?

While it is common for abstracts to be delayed till the day of the presentation for groundbreaking or late-breaking research, there is no reason why an abstract with the main findings from the PIVOT trial should not have been released.

A cooperative study sponsored by government institutions such as the VA/NCI/AHRQ should be prepared to disseminate data, or else why present it at AUA?

Instead, the problem may be more due the fact that Dr Wilt, as Scott Hensley pointed out in his NPR blog post, has not submitted a manuscript of the data he presented at AUA for publication, so may be trying not to fall foul of the so-called “Ingelfinger rule” that medical journals insist upon.

This rule was named after the New England Journal of Medicine editor who established it.  In its simplicity, it states that data will not be accepted for publication if it has been published elsewhere.

However, with no disrespect to a full Professor of Medicine at a major medical school who has published numerous papers, it’s unfair to the scientific community to want to have your cake and eat it  i.e. have the glory of a plenary presentation without allowing the scientific community to use the data until you get round to writing a paper.  Clearly, it would have made more sense to have a manuscript in press before agreeing to present at the AUA plenary.

I am also troubled by the fact that what constitutes publication of the data does not include presentation at the plenary session of a major scientific congress.  If this isn’t publication, what is?  While technically a plenary presentation is not a peer-reviewed publication in the sense of having been through the rigors of a journal’s peer-review process (the value of which may not be as much as we believe), there is some implied peer review of scientific merit, or else why would it be given a plenary?

According to the Journal of the American Medical Association (JAMA) policy on dissemination of information, it’s OK to make a presentation at a scientific meeting, but not to disseminate further information to the media or the press.  I’m sorry but this makes no sense to me.  In other words it appears it’s OK for Dr Wilt to present the data, but not share it, but if you were at the meeting you can report it.  However, if you were not at the meeting, then you can’t obtain a copy of what was presented?

You can read the tangled logic of the JAMA policy below, and each journal is slightly different in how it views this:

Presentation of research findings during, or publication of an abstract for, an open scientific or clinical meeting does not preclude consideration of the study for publication in JAMA.

News media reports based on coverage that occurs during the usual course of presentation of a scientific or clinical paper does not preempt a manuscript from consideration for publication.

However, authors presenting papers at such meetings are advised to refrain from providing additional information beyond that covered during the course of their presentation and exchange with meeting attendees.

Yet, here we have the results of a major 12 year study which for the first time establishes evidence based medicine on the use of radical prostatectomy in early stage prostate cancer patients, and nobody wants to share the data with the public?

In the light of the presentation that was made at the AUA plenary and the lack of any further information while we wait for Dr Wilt to submit a manuscript through the peer-review process of a major journal, which can take several months, I think it’s important for this data to be shared.

Since media reports of data presented at meetings appear to not to forego the opportunity of publishing the results, at least according to the JAMA policy, I hope that we will see further news reports about Dr Wilt’s AUA plenary presentation.

The results from the PIVOT study are important to scientists, urologists and men talking to their doctor about prostate cancer.  This data may help them better judge whether they should undertake watchful waiting or undergo radical prostatectomy surgery.  The data slides and Dr Wilt’s conclusions speak for themselves, as you can see in my earlier post.  I look forward to reading the full scientific paper when it is eventually published.

Update May 23, 2011

A webcast with audio and slides of Dr Wilt’s plenary presentation of the PIVOT data is now available on the AUA website.


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