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

Posts tagged ‘skeletal related event’

San-Francisco-Golden-Gate-Bridge-view-from-Coit-Tower-copyright-Pieter-DroppertAfter the recent JP Morgan Healthcare conference, San Francisco remains the destination of choice for forthcoming medical meetings.

Yesterday, saw the start of the 2012 ASCO Gastrointestinal Cancers Symposium (ASCO GI) at Moscone West from Jan 19-21.

In a few weeks time, the 2012 ASCO Genitourinary Cancers Symposium (ASCO GU) will be held at the San Franciso Marriott Marquis from Feb 2-4.

If you are based in San Francisco, you are at the heart of the action. It’s less optimal if you are East Coast based, unless you need the frequent flyer miles and have a good travel budget!

According to the ASCO GU preliminary program there are eight oral abstracts on prostate cancer that will be presented at the meeting on Thursday, February 2. Here’s my preview of a few that caught my attention:

ASCO GU Abstract #1:

MDV3100 Phase 3 AFFIRM trial results

The first presentation of the MDV3100 AFFIRM phase 3 trial results are a late-breaking abstract and my prediction for the highlight of the prostate cancer session at ASCO GU.

So far, all that is known from the November 3, 2011 press release from Medivation/Astellas is that MDV3100 produced a 4.8 month advantage in median overall survival compared to placebo in men with advanced prostate cancer.

This met the primary endpoint of the phase 3 AFFIRM trial, and the study was stopped early as a result.  As the press release notes, MDV3100 provided a 37% reduction in risk of death compared to placebo (hazard ratio = 0.631).

Howard Scher (MSKCC) will present the AFFIRM trial results at ASCO GU, and a closer look at the MDV3100 data is eagerly awaited.

ASCO GU Abstract #6:

Effect of denosumab on prolonging bone-metastasis-free survival (BMFS) in men with nonmetastatic castrate-resistant prostate cancer (CRPC) presenting with aggressive PSA kinetics.

Amgen are seeking a new indication for denosumab (Xgeva) in prostate cancer on the grounds that it prolongs bone metastasis-free survival in men with non-metastatic CRPC.  The supplemental Biologics Application (sBLA) for denosumab will be discussed at the Oncologic Drugs Advisory Committee (ODAC) meeting on February 8, 2012.

The results from the phase 3, 147 trial were published in The Lancet last November and showed that use of denosumab delayed time to first bone metastasis by 3.7 months and improved bone-metastasis free survival.

Sally Church on Pharma Strategy Blog wrote about the denosumab 147 data presented at the annual meeting of the American Urological Association (AUA 2011) last year.

However, the challenge that Amgen faces is that they have yet to show that use of denosumab in men with prostate cancer results in an improvement in overall survival.  While it may delay the spread of prostate cancer to the bone, the gold standard for all the prostate cancer drugs approved to date has been overall survival.

The 147 trial showed that overall survival was similar between those taking placebo and those receiving denosumab (HR 1.01; 95 percent CI: 0.85, 1.20; p=0.91). Hypernatremia and osteonecrosis of the jaw were also reported with a higher frequency in the denosumab group

It is possible that there may be updated data at ASCO GU, but most likely it will be a review of The Lancet data with some subset analysis.

The FDA Center for Drug Evaluation & Research (CDER) plans to provide a free of charge, live webcast of the February 8, 2012 meeting of the Oncologic Drugs Advisory Committee, so I am looking forward to what the committee makes of Amgen’s filing.

ASCO GU Abstract #7:

Vitamin E & the Risk of Prostate Cancer – updated results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

Eric Klein will be presenting updated results from the SELECT trial that were previously reported in the October 12, 2011 issue of the Journal of the American Medical Association (JAMA).

The data showed a 17% increase in prostate cancer risk with Vitamin E supplements. Although the program abstract advertises updated data, I’m not expecting the data to differ dramatically from last year’s JAMA paper.

ASCO GU Abstract #8:

Overall survival benefit and safety profile of radium-223 chloride (Alpharadin), a first-in-class alpha-pharmaceutical: Results from a phase III randomized trial (ALSYMPCA) in patients with castration-resistant prostate cancer (CRPC) with bone metastases.

The ALSYMPCA trial data is being presented for the benefit of attendees who did not hear Oliver Sartor’s presentation on radium-223 (Alpharadin) at the NY Chemotherapy Foundation or hear Chris Parker present the trial data at ECCO/ESMO in Stockholm. This makes strong commercial sense, especially as it’s a product that physicians in the United States may know little about.

I blogged extensively about the ALSYMPCA trial results presented last year, and had the privilege to do an interview with Chris Parker from the Royal Marsden Hospital at the 2011 European Multidisciplinary Cancer Congress (ECCO/ESMO/ESTRO) in Stockholm.

I am not expecting new data to be presented at ASCO GU on radium-223, but it will be interesting to see how the audience views a bone targeted radio-pharmaceutical that unlike denosumab, does provide an overall survival benefit.

The ALSYMPCA trial showed a significant delay in time to first skeletal-related event (SRE) of 13.6 months vs 8.4 months:

radium-223-Alpharadin-time-to-first-skeletal-related-event-ALSYMPCA-trialAND a median overall survival of 14 months compared to 11.2 months for placebo group:

radium-223-Alpharadin-overall-survival-benefit-ALSYMPCA-trialAlpharadin is on the fast track to FDA approval this year.

My conclusion:  If you plan to be at ASCO GU 2012, the prostate cancer data to watch is the first presentation of the MDV3100 AFFIRM trial results.

 

I am off to Washington DC tomorrow for the annual meeting of the American Urological Association (AUA).

If you are not able to attend, then you can follow the Twitter coverage on Pharma Strategy Blog where Sally Church (@MaverickNY) will be aggregating the tweets.  The conference hashtag is #AUA2011.  I also expect to be live-tweeting from the conference.

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Like many medical conferences in the United States, the AUA meeting kicks off with independent continuing medical education (CME) satellite symposia on topics of interest.

As a lawyer who has to pay for his own continuing legal education (CLE) credits, I have to confess that I am somewhat cynical that other professionals such as physicians expect to have their CME paid for through free industry-sponsored events.  These symposia are certainly not cheap to run.

However, compared with Europe, CME events in the United States are usually well-produced and fair balanced, albeit with a topical theme that obviously relates to the sponsor’s interest.

The two satellite symposia that I will be attending at AUA are Friday evening’s Amgen supported “Managing Skeletal-Related Events in Patients with Prostate Cancer” and the Saturday morning Astellas/Medivation supported “Reason for Hope: Key Advances in the Management of Castration-Resistant Prostate Cancer.”

While at Quintiles, I was lead CRA/European Project Manager for the phase III trial trial of risedronate in elderly women at risk of hip fracture, so I am interested in bone related treatments, and am looking forward to hearing more about denosumab (Xgeva®) and its impact on skeletal related events (SRE).

Oliver Sartor (Tulane) raises some excellent questions in a recent paper published in the Asian Journal of Andrology, “if a patient has a SRE, does it affect the way a patient feels, functions or survives?”

Sartor argues that a better definition of the benefit a drug has on SRE’s would be “a reduction in pain, analgesic consumption or improvement in quality of life (QoL)” instead of the current “feel, function or survive” standard.

He notes that patients with bone-metastatic castrate resistant prostate cancer (CRPC) have a limited life expectancy, so that QoL is a key issue. “An asymptomatic event linked to a future adverse event is less meaningful in a patient with metastatic CRPC.

Sartor concluded his paper by saying:

“The lack of effect of bisphosphonates or denosumab on patient-reported outcomes including QoL, pain or analgesic consumption continues to be a disappointment for this entire field.”

When we talk about a reduction in SRE’s what does this really mean for the patient?  I look forward to hearing what the expert panel at Friday evening’s symposia on this topic and hope it will be addressed.

Moving on to the other satellite symposium, supported by Medivation/Astellas, that I will be attending early on Saturday morning.  I expect this symposium will focus on new drugs in the pipeline such as MDV3011 and ARN-509 that target the androgen receptor. Hopefully they will also discuss other therapeutics, such as the recently approved abiraterone acetate (Zytiga®), as well TAK-700, which has a similar mechanism of action to abiraterone, i.e. they both inhibit CYP17 and testosterone production.

I’m looking forward to hearing what the expert panel has to say about the need to take prednisone with abiraterone, and whether there are any issues surrounding long-term usage if abiraterone ends up being used earlier in the pre-chemotherapy setting.  Updated data from the COU-AA-301 trial will be presented at AUA on Monday, and I expect a lot of interest from urologists in this.

The satellite symposia are set to be a good warm up act to the start of the main AUA meeting that runs from May 14 to 19 in Washington DC.  I’ll be writing more from the AUA 2011 over the next few days.

ResearchBlogging.orgSartor, O. (2011). Denosumab in bone-metastatic prostate cancer: known effects on skeletal-related events but unknown effects on quality of life Asian Journal of Andrology DOI: 10.1038/aja.2011.33

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