Sequential Sipuleucel-T Immunotherapy and Androgen Deprivation in Men with Metastatic Prostate Cancer
Sipuleucel-T is an autologous cellular immunotherapy directed against prostatic acid phosphatase (PAP) that is currently approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Two studies are currently evaluating the optimal sequencing of sipuleucel-T in the context of androgen-deprivation therapy (ADT) in patients with mCRPC. Enzalutamide is an androgen receptor inhibitor that is also approved for the treatment of patients with mCRPC.
In the ongoing, randomized, open-label, phase 2 STRIDE clinical trial, Petrylak and colleagues assessed the safety and efficacy of sipuleucel-T plus enzalutamide, administered either concurrently or sequentially in patients with asymptomatic or minimally symptomatic mCRPC(Petrylak et al. STRIDE Trial. ESMO 2014: Abstract). In the concurrent arm, eligible patients have received sipuleucel-T infusions (3 infusions at 2-week intervals) starting 2 weeks after enzalutamide (160 mg daily for 52 weeks); in the sequential arm, patients are administered sipuleucel-T infusions 10 weeks before initiation of enzalutamide therapy. The primary end point is T-cell immune response to the sipuleucel-T immunizing antigen, PA2024. A secondary end point is time to recurrence of elevated serum prostate-specific antigen level.
Overall, 52 patients had completed sipuleucel-T infusions and were available for safety and efficacy assessments. No significant differences were found between the 2 treatment arms in sipuleucel-T product parameters, including antigen-presenting cell (APC) activation, APC count, and total nucleated cell (TNC) count. The safety profiles were similar between the 2 treatment arms and are consistent with those previously reported with sipuleucel-T and enzalutamide.
The incidence of adverse events (all grades) was similar between the concurrent and the sequential arms (80% vs 96%, respectively), with treatment-related grade 3 or 4 events reported in 4 and in 7 patients, respectively.
In the second trial, known as STAND, Drake and colleagues also evaluated the optimal sequencing of sipuleucel-T and ADT in 65 men with biochemically recurrent prostate cancer who are at high risk for metastases (Drake et al. STAND Trial. ESMO 2014: Abstract 775P). The patients were randomized to receive sipuleucel-T followed by ADT 2 weeks after the third infusion, or ADT 3 months before sipuleucel-T therapy.
The primary end point is cellular immune response; the secondary end points are humoral/cytokine responses, drug parameters, and safety. Preliminary analysis of this trial indicates that sipuleucel-T induces robust immune responses to PA2024 and PAP in both arms, correlating with cumulative TNC count and maximum eosinophil count after sipuleucel-T treatment.
Taken together, the findings from these 2 clinical trials indicate that sipuleucel-T induces potent immune responses in patients with mCRPC, regardless of the ADT sequencing.