Of moonshots, precision medicine, and progress in the management of cancer

As your sitemaster, let me be very clear about a couple of my most basic beliefs about prostate cancer and prostate cancer research. I want to do this because of all the recent media discussion about Vice President Byden’s “Moonshot” and the possible wonders of precision medicine.

(1) Hope is critical and essential for those who have any form of high-risk, progressive, or metastatic cancer — prostate cancer very specifically included. Every patient with this type of cancer wants a cure, and the vast majority of clinicians and researchers who specialize in treating and seeking better treatments for such cancers want to be able to provide such cures. And we have made considerable progress since I first started to learn about prostate cancer in 1988.

(2) Most high-risk and progressive cancers — again, prostate cancer specifically included — are a long, long way from being simple diseases in which, if you shut down one or two pathways (genetic, genomic, or receptor-based) for progression of the disease, you will be able to actually eliminate the disease. Cancers can and customarily do evolve biologically in varied ways in individual patients …  and have shown a profound ability to evolve (often very fast) in ways that can circumvent our best abilities (so far) to eliminate them.

(3) We will only start to be able to “cure” prostate cancer when we are willing to accept that there are numerous things we do to our bodies today (individually and societally) — over our lifetimes, consciously and unconsciously — that increase individual risk for prostate cancer. Then we will need to stop doing those things.

(4) Even then, we are unlikely to be able to eliminate the risk for prostate cancers entirely — but we may be able to manage that risk downwards in ways that correspond to the ways we have “managed down” the risks for a wide variety of formerly devastating infectious diseases and even the risks for a wide variety of serious cardiovascular diseases.

(5) The absolute best way to be able to eliminate prostate cancer is to massively lower the risk that men are going to get it in the first place. … But the amount of really good research going into that opportunity is tiny.

From that perspective, and while, as a co-founder of Prostate Cancer International, and as the sitemaster for this prostate cancer news service, I am all in favor of increased funding for research of all sorts of different ways to help to manage the risks associated with diagnosis with and death from prostate cancer and multiple types of cancer, I am also very pragmatic about the potential inherent in the vice president’s “Moonshot” and in precision medicine (always assuming the relevant funding actually becomes available).

For the past 20+ years, I have also been a member of the Board of Directors of another cancer organization, focused on a form of cancer called multiple myeloma. In his most recent blog post to the global membership of the International Myeloma Foundation, Dr. Brian Durie — the chairman of that organization and a well-known figure in the world of myeloma research — expresses his views about the potential of the “Moonshot” and precision medicine in the context of what has been going on in the world of myeloma research and treatment, where there have been major, major advances over the past 20 years … but where we also, still, don’t have “cures” for high-risk and progressive forms of myeloma either. Much of what Dr. Durie says in that blog post is applicable to other cancers too, prostate cancer included. You might want to read it.

16 Responses

  1. Moonshot isn’t the right term for the “cure cancer” speeches from Biden. When Kennedy made the “to the moon” speech it was vey noble and a great idea that was uniting to a great country. It was a very complex journey set forward and accomplished. But there was only one moon to solve. As the Sitemaster states, cancer is a general term describing all cancers. Each cancer is in itself it’s own moonshot. I wish it was as easy as finding a single cause of cancer, but that remains an unrealistic thought.

  2. I am encouraged that we have a Moonshot program for cancer. I expect fairly rapid returns, as some of the low-hanging fruit is important. As just an illustrative instance, one of the items in the news currently is Moonshot pressure on institutions to stop sitting on results of clinical trials research. That is easy to accomplish. Indeed, one would think it is not a problem, but it is. Just try going to clinicaltrials.gov and checking for results from a number of prostate cancer trials that have been completed for some years. I have been surprised by the number of times there are no results.

  3. I noticed that par of Dr. Durie’s essay rests on research by Dr. Vinay Prasad. Frankly, bluntly, I am not impressed with some of Dr. Prasad’s work involving prostate cancer.

  4. Dear Jim:

    The fact that you are not “impressed” by some of Dr. Prasad’s work doesn’t necessarily imply that he is wrong. There is a lot of hype about the Moonshot that doesn’t impress me at all because it is based on the type of logic that will leading to funding for research of concepts that have very low chances indeed for meaningful long-term success (by which I mean extending median survival of > 50% men with metastatic prostate cancer by 5 years over what it is at present — as opposed to a month or two here or there for a small percentage of those men)

  5. Dear Jim:

    The fact that you are not “impressed” by some of Dr. Prasad’s work doesn’t necessarily imply that he is wrong. There is a lot of hype about the Moonshot that doesn’t impress me at all because it is based on the type of logic that will leading to funding for research of concepts that have very low chances indeed for meaningful long-term success (by which I mean extending median survival of > 50% men with metastatic prostate cancer by 5 years over what it is at present — as opposed to a month or two here or there for a small percentage of those men)

  6. Dear Jim:

    The fact that people don’t report results on ClinicalTrials.gov doesn’t mean that results haven’t been reported. Often results of trial — and particularly results that are negative — are only reported through posters at scientific meetings. This may say more about the nature of ClinicalTrials.gov than it does about people’s willingness to report results.

  7. The bottom line is … and will likely always be … the giant pharmaceutical companies never want a “cure” for prostate cancer, or any other cancer. This is due to the fact that money drives “big pharma”, and money (profits) will always be an over-riding factor to a cure. This is the world we live in … sad … but true.

  8. Dear David:

    Alas I need to disagree with you about this. If what you said was true, then why on Earth would some of those companies have — in the past few years — brought to market products that actually do cure (as in completely eliminate) diseases like hepatitis C in vast numbers of people and vaccines that minimize risk for cervical cancer?

    While it is certainly true that some sectors of the biopharmaceutical industry can be accused of seeking inappropriately high levels of profit from the misfortunes of patients, to accuse the entire industry of having no interest in curing disease (prostate cancer or any others) is neither justifiable or accurate. If the biopharmaceutical industry could find a vaccine that would eliminate risk for prostate cancer tomorrow, I have absolutely no doubt that it would quite certainly do so.

  9. Dear Jim:

    You might also want to read this announcement from the the DHHS and the NIH … which has nothing to do with the Moonshot and has been expected for some time now. It deals with the reporting of results of NIH-funded trials on ClinicalTrials.gov. It appears to have come out some time late on Friday.

  10. Dear Sitemaster,

    You need to wake up and smell the coffee! If Big Pharma is not all about money … then pray tell me why our drugs are so expensive? So many of the recent “super drugs” Zytiga, Xtandi, etc., have a primary active ingredient that comes from South America, especially the Amazon.That cost is less than $1.00/US per pill! Yet they charge inflated costs beyond imagination. Both of the above will cost a cancer patient between $200,000 and $250,000 for a 6 month supply! Gee, who’s getting raped?

  11. Dear David:

    I think you are missing what I said. I don’t disagree with you that many drugs are arguably extremely expensive. And it is very easy to make the argument that such costs are excessive (especially here in America where Congress has refused to let Medicare negotiate pricing). Talk to your members of Congress about that one!

    The place I disagreed with you was in your comment about drug companies not wanting to cure cancer if they could, since they have quite clearly been willing to cure hepatitis C and to minimize risk for cervical cancer.

  12. Dear Sitemaster:

    Thank you for the response, however, recent polls seem to thread a similar needle … that Big Pharma is in it primarily for the money. Google Big Pharma and you will see where I am coming from. Or, better yet, call V.P. Joe Biden.

  13. David:

    Again. What’s your point? I am not disagreeing with you about drug pricing.

  14. Regarding Reporting of Clinical Trial Results

    Sitemaster – I’m glad you linked that site about more effort to post study results. I had seen an article about that last week in the Washington Post.

    Regarding your comment about clinicaltrials.gov, I have always assumed, perhaps incorrectly, that that site would publish trial results as a matter of course after submission by researchers. My thinking was that the failure to post negative trial results was because researchers just did not submit results to clinicaltrials.gov. Are you suggesting that that government site chooses not to publish certain results, especially negative results?

  15. Regarding Big Pharma and Drug Pricing

    David, as a once heavy consumer of expensive pharmaceuticals in my personal war with prostate cancer, I am as eager as you are to see drugs that are a lot more affordable. On the other hand, I’m with Sitemaster on this one, because I’ve learned something about drug pricing, and no doubt the vast majority of poll respondents know next to nothing. Please consider the following, but before that I’ll say that, I’ll state there should be a special place in hell for the likes of greedy, sociopathic drug company executives Martin Shkreli and Heather Bresch of Mylan, their evil associates, and those like them. May they all fall upon misfortune and disgrace!!!

    But consider the drug treatment Provenge, manufactured and managed by Dendreon Corporation. As you may know, this is the first immune system drug for cancer, and it was approved by the FDA for prostate cancer. I followed it closely (helped advocate with the FDA for its approval), and was hoping for a more affordable price, such as $30,000 to $50,000 per three-infusion treatment — figures that were discussed even by the company prior to approval. However, the sticker price was set by Dendreon at about $93,000, which would mean more than $18,000 for the Medicare co-pay. I was disappointed with that pricing, but also understood. Here’s the backstory, in brief, and perhaps Sitemaster can fill in further detail.

    Provenge was Dendreon’s sole shot at income: no other products to sell, and no other potential product. All expenses to develop the drug were paid for by investors. In a challenging business environment with competitive products vying for first approval by the FDA for the same potential customer pool, and with a real chance that trial results would not be sufficiently favorable to gain FDA approval (meaning the investor money would go up in smoke), Dendreon spent about a billion dollars, with no income, prior to approval. After approval Dendreon spent about a half a billion more to ramp up to full production capacity and create the infrastructure and facilities to interact with doctors/patients. Moreover, there were/are substantial ongoing costs of doing business beyond the one-time charges to set up. All this is in the context of a patent expiration clock that is ticking, after which the drug can become produced by competitors as a generic, and an environment where alternate approaches were likely to emerge to compete for the same pool of customers (which has happened). And let’s not forget significant new expenses for research and development to make the drug a better fit for its customer pool and expand uses of the drug (both of which Dendreon did).

    Perhaps someone else can do a precise job with the business math, but for starters we have this: $1,500,000,000 (a billion and a half) just in start-up costs, divided by 50,000 potential customers at the outset, would require a price of $30,000 per patient just to recover the start-up costs — nothing for ongoing costs, nothing for R&D, and not a cent to reward the daring investors who stood a good risk of losing everything. Now that 50,000 figure, which was one estimate of potential customers I saw, would be if all patients in the target class opted for Provenge. Even if they did, after the existing pool had been serviced, the year-by-year pools of new patients would be much smaller, and with each passing year the likelihood of competition for those patients would be greater.

    How would you price Provenge? Evidently the executives of Dendreon were not able to get it quite right, because the last I heard was that Dendreon is struggling through bankruptcy, while trying to keep Provenge available.

    Would you have been willing to be one of those daring investors? I thank God for them, but that game was too rich by far for me!

    I don’t know about the pricing of Xtandi and Zytiga, both of which I believe benefited from some US government investment. Perhaps one of us can share those stories.

  16. Dear Jim:

    The original idea was always that researchers would routinely report their results on the ClinicalTrials.gov web site. However, “the Government” (in case you hadn’t noticed) is not exactly well resourced when it comes to policing such matters, and for some rather obvious reasons the NIH would rather spend its available (and recently rather lower) funding on new research than on being a policeman. Thus, many researchers simply didn’t post their results (which can sometimes require considerable effort if there are no formally published data to link to) — especially if those data were negative — and the NIH wasn’t exactly standing over people and telling them they “had to”.

    It is my understanding that, with the expected increase in NIH funding for 2017, the NIH will now be more rigorous in policing the posting of data. However, I don’t expect miracles. We pile more and more “paperwork” on people all the time, and (again for obvious reasons) most of us tend to avoid every scrap of it that we think we can get away with not doing.

    “The government” has nothing to do with decisions about what data to post to ClinicalTrials.gov on a routine basis — although I assume they could have if they thought that what was getting posted there was misleading. The decision about what to post from a specific study is — as I understand it — up to the NIH grant recipient (i.e., the principal investigator). The NIH does, however, provide detailed guidance about the expectations (more “paperwork”)

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