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Posts tagged ‘Alpharadin ALSYMPCA’

The abstracts for the forthcoming American Society of Clinical Oncology 2012 Genitourinary Cancers Symposium (ASCO GU) have been released and offer insight into some of the new data that will be presented at the meeting.

radium-223 Alpharadin Prostate CancerThe results of the phase III ALSYMPCA trial for radium-223 (Alpharadin) in prostate cancer were presented at ECCO/ESMO last September by Dr Chris Parker.

As expected, there is no change to data presented in Stockholm that showed radium-223 (Alpharadin) improves both Overall Survival and Skeletal Related Events:

radium-223 Overall Survival Benefit
median 14.0 vs 11.2 months; P value = 0.00185; HR = 0.695

radium-223 time to first SRE 
median 13.6 vs 8.4 months; P value = 0.00046; HR = 0.610

However, the meeting abstract published today shows that radium-223 in bone-metastatic castration resistant prostate cancer patients (CRPC), not only significantly prolonged time to first skeletal related event (SRE), but significantly prolonged 3 out of the 4 SRE components:

  • time to spinal cord compression,
  • time to pathological bone fracture
  • time to external beam radiation

No significant improvement in the SRE component of time to surgical intervention was seen with radium-223.

Subscribers to Premium Content can login to read commentary by Dr Oliver Sartor on the clinical significance of this data:

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Times-Square-NYC-November-11-2011This morning the 8am session at the Chemotherapy Foundation Symposium (The Greenspan Meeting) in NYC featured a review of current developments in Prostate Cancer.

The informative 1.5 hour session covered a lot of ground with the presenters reviewing clinical data for:

  • Radium-223 Chloride: a new option for CRPC (Oliver Sartor)
  • Pomegranite extract for Rising PSA (Michael Carducci)
  • XL184 in mCRPC (David Smith)
  • Optimizing patient selection for sipuleucel-T (Simon Hall)
  • Intermittent androgen suppression for prostate cancer (Laurence Klotz)
  • Lenolidomide/docetaxel in CRPC (Daniel Petrylak)

Oliver-Sartor-MD-presenting-at-NYC-Chemotherapy-Foundation-Symposium-2011The highlight, in my opinion, was Oliver Sartor’s excellent presentation on radium-223 chloride (Alpharadin) in which he cogently outlined its mechanism of action.  He explained that radium-223:

  • targets osteoblastic bone metastases by acting as a calcium mimic
  • is a bone-seeking calcium mimetic that binds to hydroxyapatite
  • has preferential uptake in areas of new bone formation

As mentioned previously on this blog, there are critical differences between an alpha emitter such as radium-223 and other bone-seeking radiopharmaceuticals that are beta emitters.

Sartor presented some excellent slides that showed how alpha emitters require much fewer DNA hits to kill cells, are short range and have a higher initial energy per particle.  In other words they are very effective at short range within the bone microenvironment, something that Chris Parker from The Royal Marsden Hospital mentioned in his interview from ECCO/ESMO in Stockholm.

Sartor concluded his Chemotherapy Foundation Symposium presentation by reflecting on “where do we go from here” in prostate cancer?  Some of his observations were:

  • We are currently in a sequencing paradigm. Drug A then B then C
  • We need to combine active agents to give the best results, that is our next challenge
  • How are we going to afford it all?

Sartor succinctly highlighted where the rubber currently hits the road, and left the audience with plenty to reflect upon. I am sure we can expect further debate on sequencing and combination possibilities at medical and scientific meetings in 2012.

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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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I will be flying to Stockholm next week for the European Multidisciplinary Cancer Congress (twitter #EMCC2011), more commonly known as ECCO or ESMO 2011.

What are the sessions that look interesting at the meeting? I previously wrote about the phase III ALSYMPCA trial data for Alpharadin that will be presented as a late breaking abstract.

In addition, the best abstract at ECCO 2011 is on vismodegib in basal cell carcinoma.  Sally Church on Pharma Strategy Blog has written extensively about the hedgehog pathway and role of smoothend inhibition in the treatment of cancer.

What else has attracted my attention at ECCO 2011 in Stockholm? In looking at the preliminary program I was struck by the large number of scientific symposia throughout the meeting. However, many occur at the same time! On Saturday 24th two in particular caught my attention:

Molecular Imaging of Hypoxia

Nanotechnologies for Targeted Drug Delivery

Having written about hypoxia and nanotechnology on this blog, I will probably go to one of those two sessions.

Later in the conference, there is another block of scientific symposia on Monday 26th, again all at the same time! Several that look particularly interesting include:

  • How to understand and to Reverse Drug Resistance in Metastatic Breast Cancer
  • From New Targets to New Drugs in Prostate Cancer
  • Tailoring Personalized Medicine for the Future
  • The Role of IGFs/IGF-1R Pathway in Paediatric Malignancies

And in case one still hasn’t had enough science, there’s another group of scientific symposia on the final day of the conference on Tuesday, 27 September including:

  • Unravelling Ras PI3 Kinases Targets 
  • PARP inhibiting strategies: from Molecular Mechanisms to Rational Clinical Applications

I expect Stockholm to be expensive, they jokingly say you can buy a brewery in America for the price of a beer in the city, but it looks like there’ll be some interesting news and scientific data from the meeting. Hopefully I’ll have a few hours sometime to see something of what looks like a stunningly beautiful city.

If you plan to be in Stockholm do let me know. I can be reached via twitter (@3NT).

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