There are no major presentations of phase III clinical trial data at the European Association of Urology (EAU)
No new data on radium-223 (Alpharadin) was presented at the European Association of Urology 2012 Congress in Paris today.
Dr Chris Parker presented a poster with similar data to his oral presentation on Alpharadin at the recent ASCO GU meeting. The phase III ALSYMPCA trial results were first presented at ECCO/ESMO in Stockholm last year.
However, one of things I did learn at EAU12 was that Bayer have opened an Expanded Access Program for Alpharadin, that allows eligble advanced prostate cancer patients access to this radiopharmaceutical pending regulatory approval.
I was told by a Bayer representative that a license is required but that they are now approving sites so that they can administer Alpharadin in the United States pending regulatory approval.
Further information is available about the trial (NCT01516762), and inclusion/exclusion criteria are available on the clinicaltrials.gov website. This is good news for advanced prostate cancer patients.
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.
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:
This 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)
The 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.
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.
At 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.
What 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.