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Posts tagged ‘European Association of Urology’

Arc de Triomphe, Paris

Scenes from EAU - Arc de Triomphe

Here at the European Association of Urology (EAU) congress in Paris, there are some interesting debates amongst delegates attending the meeting regarding new therapies either recently – or about to be approved – for castrate-resistant prostate cancer (CRPC).

For example:

  1. How should abiraterone and MDV3100 be sequenced pre or post chemotherapy?
  2. Would combining the two drugs post chemo be a better strategy that leads to superior outcomes?
  3. Where does chemotherapy fit into this emerging paradigm?  Do we need chemotherapy in an new era of oral therapies?  If yes, which patients should be considered eligible?
  4. How will immunotherapies such as Provenge be used once approved – before or after abiraterone in the pre-chemo setting, but likely not together given the steroid component?

Reimbursement remains a challenge in Europe

Now, these are all valid clinical questions, but there is an elephant in the room that isn’t being discussed so far (Dendreon got a lot of stick over the US price last year, which was publicly considered ‘very expensive’ or ‘too expensive’ by many thought leaders for Europe), namely, reimbursement.

Consider that the US wholesale price for Provenge is $93K and abiraterone is ~$48K, depending on how many months are needed (likely more in the pre-chemotherapy setting), you can already see that both sequencing and combinations are going to take the economic costs much higher for European health care systems.  That’s without figuring in the price for MDV3100 and Alpharadin, which have not been filed yet or cabazitaxel, which costs around $42K in the US depending on the number of cycles taken (from memory).

However, with Taxotere now generically available, it’s not hard to imagine many centres repeating docetaxel in second-line if the patient had a good response rather than administer the more expensive cabazitaxel.  In general, though, there is little doubt that the impact of either sequencing therapies, or using in combination, will add to the cumulative cost of treatment in an upwards manner.

The bigger questions for Europe in this scenario then become:

  • How to best manage available resources from the allocated healthcare pot?
  • The majority of money in cancer care is spent on the last 6 months of people’s lives – how should that be addressed ethically, economically and medically?

By the way, for American readers of this blog, please don’t call European provision ‘socialist healthcare’ – this is a silly misnomer, because:

  • It isn’t free – people pay for it – it’s deducted at source from wages in most countries
  • Several EU members such as the UK have a conservative, not socialist, Government in power
  • In Germany, a model of private providers similar to the US exists, and even in the UK additional private care can be bought through an employers offering, proving that not all European countries provide healthcare in the same way.

Abiraterone will likely be reimbursed at a discount in the UK

Meanwhile, J&J’s abiraterone is an interesting case study in point.  While approved by the EMA/CHMP, it isn’t available in all EU countries yet, as it wenders its way through the reimbursement approval process.  As I understand from delegates here, it is available in Ireland, for example, but was rejected by NICE in the UK as ‘too expensive’.

What was interesting here at EAU was learning from some EU thought leaders and competitor manufacturers that Janssen have apparently negotiated a discount of 40% of the list price in order for it to be available in the UK, although nothing official has been announced yet.

Will UK pricing have a broader impact on continental Europe?

Given the severe pan Europe economic hardship at present, one wonders how low this pricing strategy might go given that Greece is usually the lowest priced country.  If the 40% discount being bandied about here at EAU is correct, will other other EU countries look at the UK price and demand a similar discount?  It’s one thing the UK and say, Spain and Greece being 10-20% lower than Germany, but nearly half the price might upset the natural basket negotiations and wheeler dealing that usually occur.

You can almost imagine a satirical cartoon in Private Eye or The Economist, whereby jaundiced eye balls loom eerily out of a map of Europe, as each country warily looks at its usual reference baskets.

It will be interesting to watch what happens in the near future, because what happens in the advanced prostate cancer arena may have broader implications, not only for all EU countries, but also other manufacturers in the cancer marketplace.  Everyone involved is going to be following this evolution carefully.

 

EAU-2012-Congress-Paris-View-of-Eiffel-Tower-By-NIght

Sights of 2012 EAU Congress

Greetings from the European Association of Urology (EAU) congress in Paris. Despite the grey drizzle typical of Europe in winter, this is actually quite an interesting meeting with lots of poster presentations.

One poster that caught my eye yesterday was from Martin Gleave’s group on clusterin knockdown synergising MDV3100 activity. Previously, we discussed on this blog how inhibiting clusterin with custirsen (OGX-011) potentiated docetaxel. At the AUA meeting last year, the issue of whether the same would happen with MDV3100 was suggested, as you can see in the short video blog.

Clusterin is also known as testosterone-repressed prostate message-2 or TRMP-2, and has been shown by Miyake et al., (2000) to be important in advanced prostate cancer. This is because the treatment of choice in hormone-sensitive disease, androgen deprivation therapy (ADT), can lead to clusterin upregulation, thereby causing castrate resistance.

The group’s latest study at EAU looked at whether clusterin knockdown sensitised MDV3100 activity and evaluated potential mechanisms for how this might work.

The results showed that:

  1. Neither MDV3100 or custirsen alone affected AR levels, but in combination, the AR protein levels were reduced.
  2. The combination synergistically suppressed LNCaP (human prostate cancer cell lines) in vitro and in vivo compared to monotherapy with either alone.
  3. Inhibition of the AR has been shown to activate the PI3K-Akt pathway, but the combination prevented this from occurring.
  4. Dual treatment also increased AR instability via decreased levels of the AR chaperone, FKBP52.
  5. AR degradation occurred with combination therapy via the proteasome, leading to synergistic repression of AR transcription.

While these data offer a very nice and logical preclinical rationale for considering a combination of MDV3100 and custirsen to overcome castrate resistance in advanced disease, we also need to see clinical evidence in advanced prostate cancer before getting too excited. I like the idea scientifically but Oncogenex, the manufacturers of custirsen, have not exactly been swift at moving their previous trials along, as Luke Timmerman noted his Xconomy article last year.

Ultimately, the proof is always in the (clinical) pudding.

References:

ResearchBlogging.orgMiyake H, Nelson C, Rennie PS, & Gleave ME (2000). Testosterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen independence in prostate cancer. Cancer research, 60 (1), 170-6 PMID: 10646870

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This weekend I’m at the annual meeting of the European Association of Urology (EAU), which takes place here in Vienna, Austria.  It promises to be an interesting meeting, with new developments in the areas of bladder/urothelial, prostate and renal cancers being discussed.

For those of you interested in following remotely, here are the links to the scientific programme and the podcasts.  You can also browse the abstracts online.

According to the EAU:

“For the 2011 edition, more than 3,700 abstracts were submitted and reviewed by the EAU Scientific Congress Office. As a result, 1,111 abstracts and 50 video abstracts were accepted, and will be presented at 92 poster sessions and 8 video sessions.”

While not as big as it’s American cousin, the AUA, that’s still an impressive number of abstracts submitted for the meeting.  They have an active presence on Twitter, you follow them via @uroweb.

I’m going to try and aggregate my thoughts and tweets from the sessions, depending upon the availability of wifi access.  Most of the sessions I’m interested in will be from Saturday to Monday.  Unfortunately, my iPad didn’t arrive in time so the iPhone and wifi will sadly have to suffice, although coverage may be spotty with thousands of people also trying to access the network.

Check back over the weekend for any live tweeting for the hashtag #EAU11 (#EAU is unfortunately used for other things, including water tweets), but you can follow the #EAU11 coverage in the widget below:

If any one has any questions or observations, please do add them in the comments below.

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