Does sequencing of therapy affect outcomes of treatment with sipuleucel-T + ADT in high-risk disease?


We still have very little knowledge about whether early prostate cancer immunotherapy with sipuleucel-T (Provenge) or other forms of immunotherapy might be beneficial in the management of patients with high-risk prostate cancer.

A presentation to be given by Kibel et al. at the upcoming annual meeting of the American Urological Association will address available data from the co-called STAND trial, designed to evaluate the optimal sequencing of treatment with sipuleucel-T and androgen deprivation therapy (ADT) in men with high-risk, biochemically recurrent prostate cancer and a PSA doubling time of ≤ 12 months. (See abstract MP87-15 in the Prostate Cancer: Advanced III session.)

In this trial, patients were randomized (1:1) to either

  • Arm 1: sipuleucel-T followed by ADT or
  • Arm 2: ADT followed by sipuleucel-T

Regardless of the treatment arm, the initial intent was that all patients would to receive three doses of sipuleucel-T and 12 months of ADT.

Patient response was measured in terms of PSA responses over time, defined as follows:

  • PSA50 was defined as a decrease in a patient’s PSA level from baseline of ≥ 50 percent (confirmed ≥3 weeks later)
  • PSA90 was defined as a decrease in a patient’s PSA level from baseline of ≥ 90 percent (confirmed ≥ 3 weeks later).
  • PSA recurrence was defined as at least two serial rises in PSA (≥ 2 weeks apart) and a PSA ≥ 0.2 ng/ml for men who had had a prior radical prostatectomy, or ≥ 2.0 ng/ml for men with prior radiation therapy alone, and was measured from the date of the last ADT injection.

Here are the core study results as of August 2014:

  • 68 patients were randomized (n = 34 per arm).
  • The average (median) PSA levels at baseline were
    • 3.5 ng/ml for men in Arm 1
    • 2.3 ng/ml for men in Arm 2
  • 32/68 patients (47 percent) had 24 months of follow up.
  • At the nadir of PSA response levels,
    • PSA50 was observed in 100 percent of men in Arm 1 and 97 percent of men in Arm 2.
    • PSA90 was observed in 88 percent of men in Arm 1 and 91 percent of men in Arm 2.
  • At 1 year after the last ADT injection,
    • PSA50 was observed in 75 percent of men in Arm 1 and 75 percent of men in Arm 2.
    • PSA90 was observed in 50 percent of men in Arm 1 and 63 percent of men in Arm 2.
  • Among men who had completed the study,
    • PSA recurrence was observed in 8/16 men in Arm 1 (50 percent)
    • PSA recurrence was observed in 11/16 men in Arm 2 (69 percent).
    • The average (median) time to PSA recurrence was 16.7 months for men in Arm 1.
    • The average (median) time to PSA recurrence was 14.9 months for men in Arm 2.
    • Evidence of metastatic disease was seen in 3/16 men in Arm 1 (19 percent).
    • Evidence of metastatic disease was seen in 2/16 men in Arm 2 (13 percent).
  • Available data as of August 2014 show no statistically significant differences between treatment arms in any outcome.
  • Two Grade 3 treatment-related adverse events were reported in Arm 2 (fatigue and dyspnea).

The authors conclude that the combination of sipuleucel-T + ADT has shown durable PSA responses in this small cohort of patients regardless of treatment sequence. Whether these patients would have done equally well on ADT alone, without the addition of sipuleucel-T, remains unknown.

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