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. 2023 Jul 5;29(13):2426-2434.
doi: 10.1158/1078-0432.CCR-22-3832.

Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials

Emmanuel S Antonarakis  1 , Sumit K Subudhi  2 , Christopher M Pieczonka  3 , Lawrence I Karsh  4 , David I Quinn  5 , Jason M Hafron  6 , Helen M Wilfehrt  7 , Matthew Harmon  7 , Nadeem A Sheikh  7 , Neal D Shore  8 , Daniel P Petrylak  9
Affiliations

Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials

Emmanuel S Antonarakis et al. Clin Cancer Res. .

Abstract

Purpose: We present long-term outcomes from 2 randomized studies [STAMP (with abiraterone, NCT01487863) and STRIDE (with enzalutamide, NCT01981122)] that were performed to study the impact of sequential or concurrent administration of androgen receptor-targeting agents (ARTAs) on sipuleucel-T immune response and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC).

Patients and methods: Sipuleucel-T was administered per current prescribing information. Results from STRIDE are presented together with updated STAMP results. Survival status of patients was updated using demographic information to query the National Death Index (NDI). Kaplan-Meier methodology was used to analyze survival.

Results: Updated data reduced patient censoring in each study compared with the original analyses; the 95% confidence intervals (CIs) for OS are now estimable. Updated median OS (95% CI) is 33.3 (24.1-40.7) months for STAMP and 32.5 (26.0-45.1) months for STRIDE. There was no notable impact on median OS [HR, 0.727 (0.458-1.155); P = 0.177, reference = STRIDE]. OS with sequential administration was similar to concurrent administration [NDI update: HR, 0.963 (0.639-1.453); P = 0.845, reference = concurrent arm]. Sipuleucel-T potency, measured as antigen-presenting cell (APC) activation, was higher in subsequent infusions compared with the first infusion. Humoral responses (IgG + IgM antibody titers) to PA2024 and prostatic acid phosphatase were significantly elevated versus baseline. No new safety signals were observed.

Conclusions: Median OS was consistent regardless of whether the agents were administered sequentially or concurrently, including after NDI update. Results suggest that sipuleucel-T induces an immunologic prime-boost effect after initial sipuleucel-T exposure, even when combined with ARTAs.

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Figures

Figure 1. Study designs for STAMP (A) and STRIDE (B). The 2 studies have broadly similar study designs but examined different agents: abiraterone acetate + prednisone (STAMP, NCT01487863) and enzalutamide (STRIDE, NCT01981122). Patients were screened and randomized to one of 2 treatment arms: concurrent or sequential treatment. Concurrent treatment involved receiving the agent of interest from week 0 for abiraterone acetate plus prednisone or starting with a 2-week run-in (week 2) period for enzalutamide. Sequential treatment involved starting the treatment of interest at week 10. Sipuleucel-T infusions were administered at weeks 0, 2, and 4. In STAMP (A), patients received 26 weeks of treatment with abiraterone acetate plus prednisone, leading to the end of study at week 30 for the concurrent arm and week 40 for the sequential arm. Patients were instructed to take abiraterone acetate (4× 250-mg tablets) and prednisone (2× 50-mg tablets) daily. In STRIDE (B), after a 2-week run-in period, patients received 52 weeks of treatment with enzalutamide, leading to the end of the study at week 56 for the concurrent arm and week 66 for the sequential arm. Enzalutamide was supplied as 40-mg tablets with the instructions to take 4 tablets every day. Subsequently, survival was assessed during each study visit during active follow-up and every 3 months during long-term follow-up for the duration of the study or until the subject's death, whichever came first. For this updated report, the NDI was queried to get updated information on the outcomes of patients with living or unknown status as of the end of the study.
Figure 1.
Study designs for STAMP (A) and STRIDE (B). The 2 studies have broadly similar study designs but examined different agents: abiraterone acetate + prednisone (STAMP, NCT01487863) and enzalutamide (STRIDE, NCT01981122). Patients were screened and randomized to one of 2 treatment arms: concurrent or sequential treatment. Concurrent treatment involved receiving the agent of interest from week 0 for abiraterone acetate plus prednisone or starting with a 2-week run-in (week 2) period for enzalutamide. Sequential treatment involved starting the treatment of interest at week 10. Sipuleucel-T infusions were administered at weeks 0, 2, and 4. In STAMP (A), patients received 26 weeks of treatment with abiraterone acetate plus prednisone, leading to the end of study at week 30 for the concurrent arm and week 40 for the sequential arm. Patients were instructed to take abiraterone acetate (4× 250-mg tablets) and prednisone (2× 50-mg tablets) daily. In STRIDE (B), after a 2-week run-in period, patients received 52 weeks of treatment with enzalutamide, leading to the end of the study at week 56 for the concurrent arm and week 66 for the sequential arm. Enzalutamide was supplied as 40-mg tablets with the instructions to take 4 tablets every day. Subsequently, survival was assessed during each study visit during active follow-up and every 3 months during long-term follow-up for the duration of the study or until the subject's death, whichever came first. For this updated report, the NDI was queried to get updated information on the outcomes of patients with living or unknown status as of the end of the study.
Figure 2. Kaplan–Meier estimates of OS in patients who received an ARTA along with sipuleucel-T, either concurrently or sequentially. Plots of Kaplan–Meier estimates of OS by treatment arm [concurrent (— red solid line) or sequential (- - - blue dashed line)] for STAMP (NCT01487863; abiraterone acetate + prednisone and sipuleucel-T; A) and STRIDE [NCT01981122; enzalutamide and sipuleucel-T (concurrent — red solid line) or sequential (- - - blue dashed line); B]. Plot of Kaplan–Meier estimates of OS by agent as presented by study (C), collapsed across treatment arms within each study: STAMP (— red solid line) and STRIDE (- - - blue dashed line). D, Plot of Kaplan–Meier estimates of OS by treatment paradigm: concurrent (— red solid line) and sequential (- - - blue dashed line). Numbers remaining at risk are presented. Abbreviations: Sx, number of subjects included; Ev, number of events (death); Ce, censored as was lost to follow-up.
Figure 2.
Kaplan–Meier estimates of OS in patients who received an ARTA along with sipuleucel-T, either concurrently or sequentially. Plots of Kaplan–Meier estimates of OS by treatment arm [concurrent (— red solid line) or sequential (- - - blue dashed line)] for STAMP (NCT01487863; abiraterone acetate + prednisone and sipuleucel-T; A) and STRIDE [NCT01981122; enzalutamide and sipuleucel-T (concurrent — red solid line) or sequential (- - - blue dashed line); B]. Plot of Kaplan–Meier estimates of OS by agent as presented by study (C), collapsed across treatment arms within each study: STAMP (— red solid line) and STRIDE (- - - blue dashed line). D, Plot of Kaplan–Meier estimates of OS by treatment paradigm: concurrent (— red solid line) and sequential (- - - blue dashed line). Numbers remaining at risk are presented. Abbreviations: Sx, number of subjects included; Ev, number of events (death); Ce, censored as was lost to follow-up.
Figure 3. APC activation box-and-whisker plot of APC activation illustrating impact of each sipuleucel-T infusion in patients with at least one infusion of sipuleucel-T in STAMP (A) and STRIDE (B) studies by treatment group: sequential (blue) and concurrent (red). A different form of A has been presented previously (23). These results indicate there is evidence of an immunologic prime-boost effect given the greater ex vivo APC activation after both the second and third infusions relative to that after the first infusion.
Figure 3.
APC activation box-and-whisker plot of APC activation illustrating impact of each sipuleucel-T infusion in patients with at least one infusion of sipuleucel-T in STAMP (A) and STRIDE (B) studies by treatment group: sequential (blue) and concurrent (red). A different form of A has been presented previously (23). These results indicate there is evidence of an immunologic prime-boost effect given the greater ex vivo APC activation after both the second and third infusions relative to that after the first infusion.
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