Should immunotherapy be administered before or after hormone therapy?

This study examined whether immunotherapy with sipuleucel-T (Provenge) shows a greater immune response if administered before or after androgen deprivation therapy (ADT). Authors present preliminary evidence of improved immune cell response when sipuleucel-T was administered first in patients with recurrent prostate cancer at high risk of progression.

It has been estimated that about 20 to 40% of men will show disease recurrence after primary treatment for localized prostate cancer. Recurrence is typically measured with blood tests based on rising PSA levels (prostate specific antigen; a protein elevated in the blood in prostate cancer). Some men are at increased risk of rapid disease progression, such as cancer spreading to distant organs (metastatic disease).

ADT is a type of hormone therapy often prescribed for patients at high risk of progression. ADT targets male sex hormones (such as testosterone) active in cancer growth. However, many men stop responding to ADT over time. Previous studies have shown improved treatment response when ADT was combined with immunotherapies. Immunotherapies boost the patient’s own immune system to recognize and destroy cancer cells. Sipuleucel-T is a therapeutic vaccine manufactured from the patient’s white blood cells. The optimal timing of ADT and immunotherapy for high-risk disease has not been fully studied.

The aim of this study was to examine whether sipuleucel-T is best administered before or after ADT for men with recurrent prostate cancer at high risk of progression.

68 men with recurrent prostate cancer at high risk of progression to metastatic disease were included in this study. All men had rising PSA levels after primary therapy for localized prostate cancer. All men received three sipuleucel-T infusions and at least 12 months of ADT. Men were randomly assigned to either undergo ADT first or sipuleucel-T first. Immune cell levels measured treatment response. Patients were followed for an average of 26.8 months.

Both treatment groups were associated with a significant increase in immune response. This was maintained at 24 months. PSA levels before treatment did not affect the level of treatment response (based on immune cells levels).

Overall, no significant differences in treatment response were observed between the two different timings of treatment. However, at 6 weeks, immune responses were significantly higher (about 2-fold higher) among men receiving sipuleucel-T first.

Recurrence after treatment (based on PSA levels) occurred in 71% of men in each group during the study period. The average time until progression was 21.8 months (sipuleucel-T first) and 22.6 months (ADT first). A higher immune response significantly increased the time until progression.

Overall, sipuleucel-T and ADT were well-tolerated, regardless of timing. Authors noted no new safety issues.

Authors concluded that administering sipuleucel-T before ADT may improve immune cell response compared to the reverse sequence.

Further studies are needed comparing sipuleucel-T plus ADT versus ADT alone to draw conclusions about its added benefit.