PURPOSE:Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC). EXPERIMENTAL DESIGN:Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated. RESULTS:Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization. CONCLUSIONS: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated.
RCT Entities:
PURPOSE:Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC). EXPERIMENTAL DESIGN:Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated. RESULTS: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-Tpatients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-Tpatients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-Tpatients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization. CONCLUSIONS: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated.
Authors: Lauren V Wood; Antonio Fojo; Brenda D Roberson; Meghan S B Hughes; William Dahut; James L Gulley; Ravi A Madan; Philip M Arlen; Marianna Sabatino; David F Stroncek; Luciano Castiello; Jane B Trepel; Min-Jung Lee; Howard L Parnes; Seth M Steinberg; Masaki Terabe; Julia Wilkerson; Ira Pastan; Jay A Berzofsky Journal: Oncoimmunology Date: 2016-07-01 Impact factor: 8.110