Summary: I’m crossing posting this piece from Dr. Len’s Cancer Blog http://www.cancer.org/aspx/blog/Comments.aspx?id=353

because it seems to me a very wise and balanced assessment of what Provenge means—and doesn’t mean—for patients, for Medicare and for society as a whole. I’ve highlighted some sentences, and inserted a few comments in italic. Many thanks to HealthBeat reader Greg Pawelski for calling attention to this piece.

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Today’s announcement by the Food and Drug Administration (FDA)   (FDA) that they approved Provenge for the treatment of advanced, hormone resistant prostate cancer is significant for several reasons, not the least of which that it offers new hope to men with advanced prostate cancer where progress in treatment has been very slow in coming.

 

Equally important, it closes the door on decades of unfulfilled hopes that tumor vaccines and immunotherapy would eventually play a significant role in cancer treatment.  We now have a demonstrated success, which is especially important given the many near-misses that have occurred over the years.  This reinforces for many the dream that one day we would be able turn on the body’s own defense mechanisms as one more approach to treat (or one day—perhaps—prevent) certain cancers.

 

As exciting as this announcement is, and with all of that hope it brings to patients, their families and the physicians who treat them, it is important that we keep this development in perspective for what it is: one small step in an otherwise complex and still difficult situation.  It is not a miracle cure, especially for men with very advanced, symptomatic disease.

 

Provenge is a brand new type of cancer treatment made by taking immune white cells from a man’s body, then exposing those cells to a stimulating agent.  After processing, those cells are then infused intravenously back into the man in 3 separate doses, each 2 weeks apart.  

 

According to the FDA, Provenge extends the lives of men with advanced prostate cancer by a little more than four months compared to men who did not receive the vaccine.

 

The side effects from the treatment are relatively modest.  The most common ones—which occurred in over 1 out of every 6 men treated—include chills, fatigue, fever, back pain, nausea, joint ache, and headache.  7 out of 10 men had an acute reaction as a result of their infusions.  These reactions included respiratory problems such as bronchospasm (similar to an asthma attack), but in 95% of the men who had those reactions they were considered mild or moderate according to the FDA. A little over 1 in 100 men had to be hospitalized to treat these acute reactions.

 

One of the key issues that has to be kept in mind is that this treatment—called “autologous cellular immunotherapy”–has very limited indications for use. 

 This treatment will only be available for men whose disease has progressed despite hormone treatments.  And, the men have to either be free of symptoms or have only minimal symptoms at the time of treatment. 

 

It is unlikely that men who do not meet these criteria will be able to receive the treatment since there is only one company that makes it, and I suspect that they are going to supply the treatment only to men who clearly meet the indications.  There is no possibility here that you will be able, for example, to get this from someone through the internet much like you can with certain other medications.

 

Inevitably, men (and their families) who have very advanced disease and may actually be near death are going to hear about this treatment and believe that something special has come along in their time of need.  Unfortunately, that is not the case, and their hopes should not be raised as a result of this announcement. [Already, the press has begun to hail Provenge as a “breakthrough” in headlines that will inevitably raise false hopes. See Gary Schwitzer comment on Health News Review. http://www.healthnewsreview.org/blog/2010/04/usa-today-story-gives-good-context-on-provenge-prostate-ca-vaccine.html  I agree with Schwitzer—Liz Szabo’s USA Today story (which I quote in my post below) stands out because it puts Provenge in context.]

 

One of the interesting observations about Provenge is that it did not the delay the time it took for the prostate cancer to progress in the clinical trials done to study the effectiveness of the treatment.  Despite this lack of effect on disease progression, as noted above Provenge did increase the survival of the men who received it by a little bit more than four months compared to men who received a placebo treatment. 

 

That lack of benefit in reducing disease burden while increasing overall survival is one of the observations that has had some of us puzzled. How the treatment can improve survival without having a visible, documented effect on slowing down the basic cancer process is not clear, but may relate to the fact that these types of treatments—where we recruit or activate the bodies own defense mechanisms—may take longer to work than what we usually see with traditional chemotherapy.

 

Another question is how the company that manufactures this treatment is going to meet the demand, which I expect will far exceed the supply available because of a difficult manufacturing and logistical process.

 

To make this treatment, a man has to undergo a procedure where his immune cells are removed from his body then have those cells sent to a manufacturing facility in a very short period of time. The company has to process the cells quickly and get them back to the man’s doctor in time to infuse them. 

 

That is a tall order under the best of circumstances.  I suspect that only a limited number of men can be treated initially, given what is certain to be a large number of men who are candidates for this treatment and will understandably be clamoring to receive it. [The problem is that only one company has the patent, giving it exclusive right to manufacture and distribute the drug. As a result, demand is all but certain to exceed supply.  This is an example of how our health care system is designed to meet the needs of those who profit from it, rather than the needs of patients.]

 

We also can’t ignore the issue of costs and how quickly insurance companies and the Centers for Medicare and Medicaid services will provide coverage for this treatment.  It is bound to be expensive, and one can only imagine the impact this is going to have on the Medicare budget given the fact that most of the men who will be candidates for this treatment are going to have Medicare coverage. [The company has decided to charge $93,000 per patient for the drug.  As at least one biotech analyst points out in my post below, if you look at the company’s balance sheet, your realize that this is far more than the company has to charge. Moreover, Medicare cannot afford to pay $93,000 per patient.. Ultimately, the government is going to have to step in and tell drug-makers that they cannot simply charge desperate whatever they think the market will bear. When someone is dying, the market will bear quite a bit, but neither Medicare nor taxpayers should shell out exorbitant prices for such drugs. Even though the drug offers the average patient only an extra four months, it is worth giving Provenge to many patients—at least for a trial period of a year or two—to learn more about it. But Medicare should cap the price it will pay at a level that allows the company to stay in business, but does not lead to “Jackpot” profits..]

 

I suspect, however, that given the fact the FDA has approved this treatment there will be limited resistance to paying for it.  But it will once again raise the question of how we spend our increasingly scarce fiscal resources, and whether a 4 month improvement in survival without demonstrated, clear impact on the actual disease itself is giving us what we expect from cancer treatments.  [Here Lichtenfield raises a question that we need to face. Perhaps such drugs should be limited to controlled randomized clinical trials—where we can learn more about them—but should not be available in the marketplace on the grounds that they provide too little benefit to the patient. Drug-makers need to be encouraged to focus on creating drugs that are affordable and provide clear benefit.] 

 

I think it is fair to say that some of us—me included—have been forced over the years to mute our enthusiasm and develop some healthy skepticism that “vaccine” or immunotherapy treatments like Provenge would ever prove helpful in cancer treatment. [It’s worth noting that Wall Street is more optimistic that Provenge will mark the fist of many immunotherapy treatments than many involved in cancer research. Wall Street tends to hype any medical advance, no matter how small.]

 

It’s not because we wanted to be skeptics.  No, in fact some of us over the years were excited by the possibilities of working with the immune systems of cancer patients to help the body’s own natural defense mechanisms fight cancer cells that for uncertain reasons escaped from those defenses in the first place.

 

We have seen decades of effort and many professional careers invested in proving the “vaccine hypothesis” without seeing successful, broadly applicable treatments.  Our own hopes have been dashed too many times.   The reality is that many studies with similar approaches have failed to produce consistent results or effective treatments. 

 

But hope springs eternal, and it appears that Provenge meets the test of success.  That will undoubtedly boost other research and clinical trial efforts in this area of investigation, including earlier stage trials in prostate and other cancers.

 

We can’t minimize the effort put forth by the company that has developed Provenge.  The road to success has been littered with barriers and obstacles, which they and their investigators have methodically overcome.  Others may have given up hope that they would ever get to this day; these folks did not.

 

There has been drama as well, particularly a couple of years ago when the FDA decided not to approve Provenge despite advice to the contrary from one of their advisory panels.  That led to considerable dispute within the prostate cancer and medical communities, including threats against some well known experts who did not agree with other experts that Provenge met the tests of success traditionally associated with cancer treatments.

 

It is important to remember that often the progress we have made in cancer treatment—especially those cancers that have proven difficult to treat, such as prostate cancer—has come in small steps with a bit of improvement here and another bit there.  Rarely does progress in therapy come in huge leaps.  Small steps are more typical, and Provenge fits into that scenario.

 

So here is a “hats off” to a new and successful approach to treating a cancer that has proven difficult to treat in its advanced stages.  And here is another “hats off” to those who had the foresight to do the research—both basic science and clinical trials—that led to approval of this novel approach, one that is truly fascinating and has significant importance and impact for the cancer treatment, research and business communities. 

 

And here’s hoping this is but the first step in a new and effective way to treat cancers that will bring much progress and success in the future.