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FDA Questions Using Avodart to Cut Prostate Cancer Risk


3 Star

FDA Questions Using Avodart to Cut Prostate Cancer Risk

Our Review Summary

This story attempts to explain why the FDA seems hesitant to approve a drug named Avodart for the prevention of prostate cancer. (It also diverges briefly into the discussion of a second drug, Proscar, which isn’t the main focus of the story and won’t be addressed in our review.) The key point — which the story communicates well — is that the drug prevents low-risk cancers but seems to encourage the growth of aggressive ones. So the the data require close scrutiny to see whether there’s an actual net benefit to patients who are treated with the medication. Unfortunately, the story fell short in its coverage of some of the other areas that we feel readers deserve to see addressed. Detail about costs and harms is especially important in a case like this where a drug’s purported benefits appear to be marginal–and yet the story provided no information.


Why This Matters

Prostate cancer is second only to lung cancer as a cause of cancer death among men in the United States. However, it is important to keep in mind that the disease is diagnosed in many more men than it kills. This is because most prostate cancer is so slow-growing that patients typically die of something else before the tumor has a chance to spread. The most pressing need, therefore, is for techniques that can identify and eliminate the aggressive tumors, which are causing the lion’s share of the death and damage. We certainly must look cautiously on any therapy that may increase the risk of these high-risk cancers, even if it prevents the low-risk ones.

A problem with research in this area is that the ultimate goal of therapy ideally should be to prevent death from cancer. However, the number of patients, years of follow-up, and costs needed to show a survival benefit are prohibitive. Consequently, studies target the more easily measured surrogate endpoint of cancer incidence–which may be a meaningless endpoint for the reasons described above.


Does the story adequately discuss the costs of the intervention?

Not Satisfactory

No costs are mentioned — not acceptable when the drug is already on the market and cost information is easily obtained. According to one estimate our reviewer found within minutes, treatment with Avodart costs about $4 per day. Previous analyses of finasteride, which has a similar mechanism of action, estimated that the cost per quality-adjusted life year (QALY) gained from treatment far exceeds $100,000/QALY. An acceptable cost effectiveness for a treatment is considered to be less than $50,000/QALY.

Does the story adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

A couple of problems here. First, the story describes the overall cancer prevention benefit for Avodart in relative terms (“a 23% reduction”) but never gives us the absolute numbers. It would have been much more meaningful if the story had told us, as the original study did, that  “659 of the 3305 men in the dutasteride [Avodart] group (19.9%) and 858 of the 3424 men in the placebo group (25.1%) received a diagnosis of prostate cancer, representing an absolute risk reduction with dutasteride of 5.1 percentage points.” (As noted above, even these absolute risk data are somewhat misleading.)

Second, a Glaxo representative makes the reasonable point that although the cancers prevented by Avodart may be slow-growing, many men with these kinds of cancers undergo invasive surgery that reduces their quality of life. To understand the scope of this benefit, however, it is important to know just how many men with these lower-risk cancers go on to receive surgical treatment, and what kinds of consequences they might avoid by taking the drug. Otherwise there’s no way to measure this benefit against the potential harms of treatment, such as increased risk of aggressive cancer and sexual dysfunction.

Does the story adequately explain/quantify the harms of the intervention?

Not Satisfactory

Use of Avodart is associated with increased risk of sexual side effects and a small increase in heart failure risk. The story didn’t mention these potential problems.

Does the story seem to grasp the quality of the evidence?

Not Satisfactory

The story gives a decent overview of what happened in the REDUCE study, which is the trial that Glaxo is using to support its application for Avodart. It’s clear that this this was a large placebo-controlled study designed to generate enough high-quality evidence to satisfy FDA standards. And it was important to point out that Avodart, despite lowering the overall risk of prostate cancer, may have increased the risk of aggressive cancers that are more likely to be lethal. The prevention benefit was for lower-risk tumors that would never have caused a problem for most men. So the overall risk-benefit calculation for this drug is more complex than it might appear at first glance.

Nevertheless, the story missed some elements that are critical to understanding the results. Notably, it didn’t explain  that the study investigators biopsied men after the 2nd and 4th years of treatment, regardless of whether their was a clinical reason (such as elevated PSA levels or an abnormal digital rectal examination) for doing so. Therefore, the cancer detection rate was substantially inflated–the 19.9% rate in the Avodart group, while lower than the placebo group, still exceeds the expected lifetime rate of about 16%. When the authors looked at cancers detected for clinical reasons–the real world experience–there was no difference in cancer detection rates.

A close one, but we feel the story did not provide enough context for readers to judge the real world importance of the findings. The story might have done a better job here had it included more independent sources in its coverage.

Does the story commit disease-mongering?


No disease-mongering here.

Does the story use independent sources and identify conflicts of interest?

Not Satisfactory

The story only delivers information from an FDA documented posted online and from a drug company spokesperson. So, in fact, we don’t hear from a truly independent voice and not from any expert in clinical care either.

Does the story compare the new approach with existing alternatives?

Not Applicable

There are no proven ways to prevent prostate cancer (although supplements such as vitamin E and selenium have been found to be ineffective), so we can’t fault this article for not mentioning any. We’ll call it not applicable.

Does the story establish the availability of the treatment/test/product/procedure?


The story makes it clear that Avodart is approved by the FDA for treatment of non-cancerous enlargement of the prostate. It also explains that Glaxo Smithkline is seeking new approval to market Avodart for the prevention of prostate cancer. The story could have been more clear about the fact that Avodart can already be prescribed off-label for cancer prevention (even though it is not officially approved for this), and that the FDA approval would sanction this existing use as well as expand it to other clinicians and patients.

Does the story establish the true novelty of the approach?


The story doesn’t try to oversell the novelty of using Avodart to prevent prostate cancer. But it could have made it clearer that the effects seen with Avodart (i.e. prevention of low-risk tumors, increased risk of aggressive tumors) are very similar to those reported previously with Proscar, a drug in the same family. This increases our confidence that the findings are a real effect and not random fluke of the data.

Does the story appear to rely solely or largely on a news release?


The story quotes an FDA document as well as an official from Glaxo. It doesn’t appear to rely solely on any press release.

Total Score: 4 of 9 Satisfactory


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