Biotech Strategy Blog

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Posts tagged ‘Prostate Cancer Vitamin E’

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.


Vitamins on Shelf

Despite promising preclinical data suggesting that selenium and vitamin E may reduce prostate cancer risk, a randomized trial started in 2001 with over 35,000 men now suggests otherwise.

Given the prevalence of people taking vitamin supplements, these findings have important public health implications.

The results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) reported in the October 12, 2011 issue of the Journal of the American Medical Association (JAMA) show that dietary supplementation with Vitamin E significantly increased the risk of prostate cancer in healthy men.

Over 35,000 men were randomized into 4 groups: selenium (200 mg/d from L-selenomethionine) with matching placebo, vitamin E (400IU/d of all rac-a-tocopherol acetate) with matching placebo, both agents, or placebo.  The study was stopped in September 2008 as a result of an interim analysis that showed lack of efficacy for risk reduction and futility analysis showed a lack of future benefit.

The data in 2008 with a median follow-up of 5.5 years suggested an increased risk of prostate cancer observed with vitamin E.  That finding has now reached statistical significance in the latest analysis of the trial data, 7 years after the last patient was randomized.

Participants were healthy men at average risk of prostate cancer. They were monitored every 6 months and recommended to undergo prostate-specific antigen (PSA) and digital rectal examination (DRE) based on the standard of care in their community.  The primary end point was prostate cancer incidence resulting from routine community care.

The updated results from the SELECT trial are published in JAMA by lead author Eric Klein from the Cleveland Clinic and colleagues.  The data shows that the incidence of prostate cancer was greater in all treatment groups compared to placebo, but statistically significant only in the vitamin E group alone (P=0.008, HR: 1.17; 99% CI, 1.004-1.36).

The authors note this data means:

 “The risk of prostate cancer at 7 years of median follow-up was increased by 17% in men randomized to supplementation with vitamin E alone, a difference that started to appear about 3 years after randomization.”

Why does Vitamin E supplementation cause this increased risk? The authors in their JAMA paper make no suggestion.

The data from this trial has important implications for all men who take multivitamin supplements.  The authors note that more than 50% of all individuals over 60 take a vitamin supplement and 23% of them take a 400 IU/d or greater dose of Vitamin E, a dose that now has been shown to increase the risk of prostate cancer.

All too often we associate taking vitamins as healthy living.  The conclusion of the authors is one that we should all take note of:

“The observed 17% increase in prostate cancer incidence demonstrates the potential for seemingly innocuous yet biologically active substances such as vitamins to cause harm.”

Only by doing clinical trials such as SELECT, can we assess the true harms and benefits of unregulated over-the-counter products such as vitamins.

ResearchBlogging.orgEric A. Klein, MD, Ian M. Thompson Jr, MD, Catherine M. Tangen, DrPH, John J. Crowley, PhD, M. Scott Lucia, MD, Phyllis J. Goodman, MS, Lori M. Minasian, MD, Leslie G. Ford, MD, Howard L. Parnes, MD, J. Michael Gaziano, MD, MPH, Daniel D. Karp, MD, Michael M. Lieber, MD, Philip J. Walther, MD, PhD, Laurence Klotz, MD, J. Kellogg Parsons, MD, MHS, Joseph L. Chin, MD, Amy K. Darke, MS, Scott M. Lippman, MD, Gary E. Goodman, MD, Frank L. Meyskens Jr, MD, & Laurence H. Baker, DO (2011). Vitamin E and the Risk of Prostate Cancer, The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA: The Journal of the American Medical Association, 306 (14), 1549-1556

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