There was just a release of some of the data from the on-going review sipuleucel-T, or Provenge, in men with early stage recurrent prostate cancer who have a rising serum prostate specific antigen (PSA) level, but who have not yet developed metastatic prostate cancer. The data wes presented by Oregon Health & Realm University Cancer Institute researchers at the 43rd Annual Meeting of the American Society of Clinical Oncologists (ASCO) in Chicago.
The study showed that Provenge did not significantly delay the time it took for a man’s PSA to reach a value of 3.0 ng/ml, the primary endpoint of the study. However, it did show a prolongation in prostate-specific antigen doubling time (PSADT). In addition, there was a trend observed in slowing the time to metastatic disease for patients who received sipuleucel-T compared with those who received placebo, but this early trend did not reach statistical significance. (We believe that the PSADT reflects the level of aggressness of prostate cancer).

“While there was no delay in the time to PSA recurrence, we did observe a slowing in the rate of rise of serum PSA in exploratory analyses. Additional follow-up is needed to determine if this effect on PSA will translate into patient benefits,” said Tomasz Beer, M.D., lead investigator, director of the Prostate Cancer Research program at the OHSU Cancer Institute; and associate professor of medicine, (hematology/medical oncology) OHSU School of Medicine.

This trial, known as P-11, is a double-blind, multi-center, randomized, placebo-controlled study involving 176 men, all of whom had prostatectomies and then had recurrent cancer as detected by a rise in the serum tumor marker, PSA. After three months of hormone therapy, 117 men received Provenge and 59 received a placebo.

As with the prior studies of Provenge, it was found to have a favorable safety profile. The most common side effects seen were fatigue, chills and fever.

The effects of sipuleucel-T on prostate cancer progression were analyzed in several ways using measurements of serum PSA. The primary analysis focused on time until the PSA reaches 3.0 ng/ml. Although there was a trend, the immunotherapy did not significantly delay cancer progression by this measure. However, investigators found the rate at which PSA was rising was 30 percent to 48 percent slower in patients who received Provenge compared to those who received placebo.

An immune monitoring protocol performed in a subset of patients demonstrated that the immune response elicited by Provenge was long-lived and still strong just prior to the booster infusion, which occurred an average of 21 months following initial treatment.. Following a booster infusion of sipuleucel-T, patients demonstrated an immune response approximately 10- to 100-fold higher than measured in placebo arm patients.

Although these results seem to be confusing and at odds with each other, I think they are actually consistent with the large phase III trial recently concluded with much sicker men. We learned from this prior trial that Provenge takes a significant amount of time to start to work and that it does not have a positive response on either PSA or on actual disease progression. However, Provenge did in this prior trial have a positive response on the length of survival, the all important “gold standard” of drug approval and efficacy. This is the number that counts.

This trial, P-11 still needs to be allowed to run its course, in other words, until men die. Sadly, this will take ten to fifteen years!

Bottom line, we need better surrogate biomarkers for survival.

In the mean time, if available, I will take Provenge even though I am an early stage recurrent prostate cancer survivor.

Joel T Nowak MA, MSW