The revised guidelines from the National Comprehensive Cancer Network for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) include multiple treatment options, such as the use of sipuleucel-T, an autologous cellular immunotherapy targeting prostatic acid phosphatase, and which is particularly useful for asymptomatic or minimally symptomatic disease. Although sipuleucel-T is now approved in the United States and in Europe for the treatment of mCRPC, the data are limited regarding the use of this agent in combination with other agents. Petrylak and colleagues presented interim results from STRIDE, an ongoing, randomized, open-label, phase 2 clinical trial designed to evaluate the concurrent administration versus the sequential administration of sipuleucel-T and enzalutamide (Petrylak D, et al. ESMO 2014: Abstract 774P).
As of the time of their presentation at ESMO 2014, 52 patients with asymptomatic or minimally symptomatic mCRPC had been randomized in a 1:1 ratio to sipuleucel-T plus enzalutamide (160 mg daily for 52 weeks) starting 2 weeks before sipuleucel-T (concurrent arm A) or to 10 weeks after the initiation of sipuleucel-T infusions (sequential arm B). Sipuleucel-T was administered as 3 infusions at 2-week intervals. The study end points were patients’ peripheral T-cell immune response to PA2024 (the immunizing antigen for sipuleucel-T) and the time to recurrence of elevated serum PSA level.
No differences were detected between the 2 arms in cytokine production, antigen presenting cell (APC) activation, APC count, and total nucleated-cell count. However, a prime boost effect on APCs was evident in both arms, as was indicated by greater APC activation at infusions 2 and 3 than at infusion 1. T-cell responses to PA2024 were observed in both arms by week 5, and immunoglobulin (Ig)G/IgM humoral immune responses to PA2024 were significantly higher at week 6 compared with at baseline in both arms. No significant differences in humoral responses were detected between arms A and B.
The nature and incidence of adverse events were similar between the arms; overall, adverse events were observed in 50% of the patients in arm A and in 61% of the patients in arm B. No grade 3or 4 treatment-related adverse events were reported in either arm. These preliminary data suggest that sipuleucel-T potency, prime boost, and safety are similar with and without concurrent enzalutamide. Of note, sequential enzalutamide does not alter the magnitude of the immune responses to sipuleucel-T. Future analyses will focus on clinical efficacy and further safety data from concurrent versus sequential treatment with sipuleucel-T plus enzalutamide.
In a related presentation, Drake and colleagues reported data from a randomized phase 2 study evaluating the optimal sequencing of sipuleucel-T and androgen-deprivation therapy (ADT) from the STAND trial, evaluating the optimal sequencing of sipuleucel-T and ADT in men with biochemically recurrent prostate cancer who were at high risk for metastatic disease (Drake C, et al. ESMO 2014: Abstract 775P).
A total of 68 men were randomized 1:1 to arm A (ie, sipuleucel-T followed by ADT 2 weeks after the last infusion) or to arm B (ADT for a 3-month lead-in followed by sipuleucel-T). All men received 3 doses of sipuleucel-T and 12 months of ADT. At the time of the ESMO 2014 presentation, 65 men had been followed for ?9 months after receiving ADT.
Sipuleucel-T induced robust cellular and humoral immune responses to PA2024 and prostatic acid phosphatase equally in both arms. The variables that correlated with the strength of the antibody responses included cumulative total nucleated-cell count and maximum eosinophil count after treatment with sipuleucel-T.
No clinical efficacy data were presented in this report. Thus, although this study did not shed light on the optimal sequencing of sipuleucel-T and ADT in these patients, it did suggest that cumulative total nucleated-cell count and maximum eosinophil count may be markers of sipuleucel-T efficacy in inducing a humoral immune response.
