Immunotherapy for men on active surveillance?


So one of the more interesting things to be announced since your sitemaster arrived at the annual meeting of the American Urological Association (AUA) in San Francisco yesterday was this one:

Dendreon sent out a media release on Friday announcing that the company plans to initiate a clinical trial of sipuleucel-T (Provenge) in some 450 men on active surveillance (AS). The so-called ProVent clinical trial will assess the efficacy of sipuleucel-T immunotherapy in reducing histopathologic disease progression in men on AS.

The ProVent trial will be a randomized, double-blind, placebo-controlled, multi-center study and will be conducted at about 50 sites across the United States. Study participants will be randomized 2:1 to receive Provenge or placebo; in other words about 300 men will be randomized to treatment with Provenge and the other 150 will be randomized to treatment with a placebo.

The primary endpoint of the trial is a histological upgrade from ISUP Grade Group 1 to Grade Group 2 or higher, or from ISUP Grade Group 2 to Grade Group 3 or higher. Secondary endpoints include the number of study participants with subsequent prostate cancer treatment (e.g., surgery, radiation, hormone therapy), the percentage of participants with a negative biopsy, and safety.

As yet there is no information about this trial on the ClinicalTrials.gov web site and so we have no information about where patients will be able to enroll in this trial if they are interested. We also have very little information about the risk for side effects associated with such treatment in what are likely to be otherwise fairly healthy patients. So patients thinking about enrolling in a trials like this must be made aware that the risks associated with treatment may outweigh the possible benefits of treatment. On the other hand, one has to acknowledge and recognize the willingness of the “renewed” Dendreon to consider implementing such a trial.

It also needs to be appreciated that the meaningfulness of data based on the proposed primary endpoint is likely to be open to some question. Would maintenance of patients at an ISUP Grade Group of 1 or 2 over time as a consequence of sipuleucel-T treatment actually “translate” into a major delay in time to invasive treatment in men who need treatment over time? This may turn out to be a hard question to answer.

As soon as we are aware of the availability of information about where patients can enrol this trial, we will be sure to let you know.

One Response

  1. Cost Practicality?

    I was on the Provenge bandwagon early, attending and giving a public session statement at the key FDA advisory committee hearing at which the committee actually recommended approval, only to be overridden by the FDA, which wanted completion of an ongoing trial to look at more data. I also participated in a rally for Provenge on Capitol Hill. I was later disappointed by the extremely high cost, though I understand the business realities that made that cost — $94,000 for the 3 course treatment as I recall — reasonable. As we know, Dendreon still had to file for bankruptcy, and I’m sure most or all of us are glad they are still in the arena and doing their best.

    I am having trouble visualizing how Provenge would be cost effective for active surveillance patients even if it were to be proven effective, and for society, especially insurance companies and Medicare. As of now, with selection of active surveillance (AS) candidates constantly improving from an already impressive level, more than 50% of AS patients never needed treatment. Use of Provenge would seem overkill for them, though of course we don’t know in advance the patients who are highly unlikely to ever need treatment (though we are ever getting a better grip on this).

    It would be beneficial, of course, if far fewer AS patients in the Provenge arm were determined to need treatment. On the other hand, with the cancer-control/cure rate very high and the side-effect burden relatively low for treatment of intermediate-risk patients, and with the cost of treatment vastly lower than for Provenge, how many empowered AS patients would be willing to fork over tens of thousands of dollars out of pocket at the start of AS even if Provenge is proven highly effective? Moreover, focal therapy is also a competitor for this pool of patients, but at a far lower cost (and, at present, somewhat murky effectiveness, which may be a lot clearer before the ProVent results are in). I’m also wondering about that patent clock, from which at least 5 more years will tick away before we have results.

    So I’m not sure of the business case here. Still, the scientist in me is looking forward to results, and I’m glad there are investors willing to foot the bill despite the risks.

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