Dendreon’s Provenge Works Best for Patients With Low PSA, Scientists Say

5/16/12Follow @xconomy

From the moment Dendreon started in business 20 years ago, most scientists have said that if its immune-booster for prostate cancer was going to work, it would probably work best at an early stage of disease, before tumors had gotten too powerful for the immune system to contain. Today, Dendreon is offering the latest slice of data that suggests that may be the case.

The Seattle-based biotech company (NASDAQ: DNDN) is announcing today a new analysis of its pivotal 512-patient study of sipuleucel-T (Provenge), which separated patients into four quartiles based on how high or low their prostate-specific antigen (PSA) scores were. The study wasn’t designed to get a statistically significant answer to this question, meaning the finding could be a fluke. Still, the results do align with what many scientists believe based on the history of clinical trials with the product—that it should work better among patients with less-aggressive forms of disease. The analysis, by lead author Gerald Chodak at Weiss Memorial Hospital in Chicago and colleagues, was posted online today on the American Society of Clinical Oncology’s website, in advance of its annual meeting.

“All of these analyses support the robustness of clinical benefit for patients, and this PSA quartile data is helpful for patients when you think about sequencing of therapy,” says Mark Frohlich, Dendreon’s chief medical officer. “The data strongly argues that using it as early as possible is the best for the patient and still allows you to go on and get other therapies.”

Dendreon won FDA approval back in April 2010 for the first-of-its-kind immune-boosting therapy, after the 512-patient study showed patients lived a median time of about four months longer on the drug than on a placebo, with minimal side effects. Since then, the company has faced a series of new competitive threats, particularly from Johnson & Johnson’s abiraterone (Zytiga) and Medivation’s enzalutamide. Those drugs are starting out by aiming to treat the sickest of prostate cancer patients, whose disease has worsened after getting chemotherapy. Dendreon’s drug is approved for patients with a less-severe form of disease, which hasn’t yet prompted them to go all the way to chemotherapy. Since prostate cancer is a slow-growing malignancy, part of Dendreon’s challenge is to persuade doctors to get more aggressive in treating patients early.

PSA, which isn’t a perfectly reliable marker, is still used almost universally by doctors and patients to track a patient’s progress. The lower the score, generally speaking, the better. In this analysis of the Dendreon study, researchers crunched the data to look at survival times of patients who entered the trial with PSA scores of less than or equal to 22.1; between 22.1 and 50.1; between 50.1 and 134; and over 134. As you can see from the chart below, Provenge patients lived longer than placebo patients in all four quartiles, but the difference in median survival times was the largest among those with lower PSA scores.

PSA of 22.1 or less PSA of 22.1-50.1 PSA of 50.1-134 PSA of 134 and up
Provenge 41.3 months 27.1 months 20.4 months 18.4 months
Placebo 28.3 months 20.1 months 15 months 15.5 months
Difference 13 months 7.1 months 5.4 months 2.8 months
–Source, Gerald Chodak et al

 

This isn’t really a surprising finding, given that Dendreon has previously said that patients with lower PSA scores had better outcomes on Provenge, about to a summary of the trial published in the New England Journal of Medicine. But it’s the first time Dendreon looked more closely at the PSA scores, by dividing patients into quartiles, Frohlich says.

Given how much debate there has always been about the data to support Dendreon’s prostate cancer drug, I’d love to hear readers thoughts on how meaningful the latest PSA analysis is. Do you think the consistency of the survival advantage in all PSA groups means something, or do you chalk this up to mere data dredging that does little more than stir up a new hypothesis? Let me know your thoughts in the comment section below.

 

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  • Akcje

    This PSA-table looks nice!! 

       This table looks nice. They should show  the raw data table of all 512 patients PSA and survival,  
    not just the selected brackets as they did.  Too easy to manipulate to make it 
    In any case it  seems good.

    But (there is always at least one :-) 
      Why did it take Dendreon so long to publish it? -It is a few minutes with computer and data… 
    So the question:   Will  this data encourage more patients than discourage (from the current label population)?In other words what is the PSA distribution or at least median among the current label-target population?  

    • Bominireal123

      The data suggests that Provenge should be approved for ealy stage use

  • Info

    How do you compare this with J&J’s Zytiga? Is Zytiga a threat to Provenge?
    Zytiga is already approved to treat advanced
    prostate cancer in patients who previously received chemotherapy.
    J&J expects to file in the second half of this year for U.S.
    regulatory approval of the drug as a treatment for men with metastatic
    prostate cancer who have not yet received chemotherapy.

  • Rob S

    One problem that comes up with immunotherapies is reduced efficacy over time. They start out strong but start to drop off after a number of months. I would need to see statistically significant data to support this claim.

    Unfortunately for Dendreon, these developments are coming too late, as the next gen of immune therapies with increased efficacy and dramatically reduced cost are coming all too soon. One example is another Seattle based company (originally), Northwest Biotherapeutics.

  • Tom

    Sadly, the ‘placebo’ group were harmed by requiring removal of their important  immune system dendritic cells via a dangerous process of leukapheresis (3.6% death rate within a couple days mostly from strokes), then not reinjecting them.   The provenge group got their cells back in a couple days after ‘training”.   Side effects (stroke) is not accounted for comparing the two groups because of the harmful placebo.  Dendrion does admit to 3% grade 5 events (death).

  • Ron in Alexandria

    Why isn’t there any data for PSA scores less than 22.1?  According to the National Cancer Institute (http://www.cancer.gov/cancertopics/factsheet/detection/PSA), PSA above 4.0 is regarded as abnormal.  Furthermore, “In one large study, however, prostate cancer was diagnosed in 15.2 percent of men with a PSA level at or below 4.0 ng/mL.”

  • Bominireal123

    Provenge has proven it is by far the best prostate cancer treatment and has by far the least amount of side affects.Mild chills and fever

  • Harold Mdlin

    My oncologist had be interviewed as a canidate for the provenge treatments.  “They” refused me treatment because I did not have a bone lesion.  In other words, one of my insurance companies (Medicare or Blue Cross) must have interviened to keep me from receiving the treatments.  Has this happened to anyone else out there?

    • JERRY RICH

      You may have to pay for it yourself…..that is what I did. Used my 401k funds

  • Studious Daughter

    Provenge is a joke.  My father was delayed chemo waiting for the Provenge to “work” as his PSA kept rising.  I’d like to see other’s posts who now have new mets while they waited the six months to see what happened.

  • ftl

    This makes perfect sense. Even without statistical significance, the trend is too smooth to ignore, and is consistent with all thoughts about how the immune system works with only a single treatment. The earlier in the disease, the more the immune system and a single target boosted by the vaccine can work. The later and more aggressive the disease the more multiple therapies should be brought to bear as the disease evolves and needs more comprehensive treatment. So long as we treat cancer with the idea of single bullet answers, the longer we will continue losing the war.

  • JERRY RICH

    I have confirmed CA with a gleason score of 6. Two years ago my PSA was doubling every year. I paid for two Provenge treatments using my own funds (insurance would not cover). My PSA is now going down dramatically, in the low single digits. I feel I added 10 good years to my life. I am 59.