Biotech Strategy Blog

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Posts tagged ‘ASCO 2012 Prostate Cancer’

Radium-223 Delays time to first SRE

At the 2012 American Society of Clinical Oncology (ASCO) annual meeting, data was presented by Dr Oliver Sartor (ASCO 2012 Abstract 4551) that showed radium-223 (Alpharadin) significantly delayed time to first skeletal-related event (SRE) in patients with castratation-resistant prostate cancer (CRPC) and bone metastases.

The SRE data for radium-223 from the ALSYMPCA phase III trial was first presented at ASCO GU earlier this year.

ASCO 2012 radium-223 data discrepancies

Algeta in a communication I received today, however, have advised that the data contained in the ASCO 2012 abstracts has “discrepancies.”  In the absence of more precise information, the discrepancies may or may not be significant.

As with good practice, the sponsors have conducted further verification of the ALSYMPCA SRE data in preparation for the US FDA NDA regulatory submission. This has resulted in changes in the numbers previously reported for SRE data in the ASCO 2012 abstracts (Abstract #4551, LBA #4512). Though discrepancies were noted, the overall interpretation of the results has not changed. The SRE data will be disclosed once all additional data verification and analyses activities are completed.

Mike Booth, Algeta Communications & Corporate Affairs, June 15, 2012 email communication.

While the message that radium-223 significantly delays time to first SRE may not have changed, data accuracy is important and should not be taken lightly.

In his ASCO 2012 prostate cancer poster discussion, Evan Yu, Associate Professor at the University of Washington, made no mention of any “discrepancy.” Instead he used the data in Sartor’s poster that showed the time to first SRE with radium-223 to be 13.6 months versus 8.4 months with placebo, a delay of 5.1 months.

Dr Parker presented updated ALSYMPCA trial data at ASCO 2012 that showed a 5.5 month delay in time to first SRE with radium-223 (12.2 versus 6.7 months). Dr Sartor’s poster was based on 541 patients on radium-223, while Dr Parker’s data was for 614 patients. This suggests that the two presentations represent data at different time points.

Were Bayer and Algeta aware of the issues at the time of ASCO and chose not to say anything?  Obviously, if the discrepancies are small or insignificant then it would not make much difference, but a large difference would be more of a concern.

What is the accurate SRE data for radium-223 from the ALSYMPCA trial?

I look forward to a future press release from Algeta/Bayer clarifying this, and hope that they will advise ASCO if corrections need to be made to the data previously presented and published.

At the 2012 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Oliver Sartor, Professor of Cancer Research and Medical Director of the Tulane Cancer Center in New Orleans told attendees in the educational session on castration-resistant prostate cancer (CRPC) that he was tired of being asked the question of what is the optimal sequence for new advanced prostate cancer drugs?

ASCO 2012 CRPC Prostate Cancer Education SessionThere is “No data,” Sartor told the ASCO 2012 audience. As a result he recommended the use of less toxic therapies first and that patients be involved in the decision making. Not quite the guidance the audience perhaps hoped for.

Sartor is, however, correct that we don’t yet have the data – the clinical trials have yet to be done that will answer the question of what is the optimal sequencing of prostate cancer drugs?

The approval of abiraterone acetate (Zytiga®) for the treatment of men with advanced prostate cancer, post chemotherapy, and the expected approval of enzalutamide (formerly MDV3100) and radium-223 (Alpharadin) have focused attention on sequencing and combination options.

A poster at ASCO 2012 showed that cross resistance may occur between abiraterone and enzalutamide, suggesting that if resistance to one develops it may lower the efficacy to the other if given subsequently. More data and research is needed to validate this finding and understand how resistance develops.

Reciprocal feedback between the PI3-Kinase and androgen receptor (AR) signaling pathways means that blocking the androgen receptor may stimulate the PI3K pathway and vice versa, leading to the tumor trying to ensure its survival. This is particularly important in prostate cancers that have the PTEN tumor suppressor gene, the result is that the targeting of both PI3K and the AR to avoid crosstalk may be required.

The scientific rationale for combining enzalutamide with a PI3-kinase inhibitor was discussed on Pharma Strategy Blog in Sally Church’s video from the 2011 American Urological Association annual meeting. Clinical trials are being planned to investigate the use of PI3-kinase inhibitors in prostate cancer.

I have written more from ASCO 2012 about the emerging challenges in prostate cancer drug development in a guest post published on Xconomy.  Many thanks to Luke Timmerman, National Biotech Editor, for the opportunity to contribute.

Hopefully, there will be more insights available at ESMO 2012 later this year and at ASCO next year on prostate cancer drug resistance, optimal sequencing and the benefits that combinations therapies may offer.

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