The phase 3b PRESIDE trial showed significant progression-free survival improvement when men with chemotherapy-naïve metastatic castration-resistant prostate cancer were treated with a regimen of continuous enzalutamide vs placebo.
Progression-free survival (PFS) improvement was observed with continuous enzalutamide (Xtandi) vs placebo plus docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer who had previously progressed on the androgen receptor inhibitor alone, according to the phase 3b PRESIDE trial (NCT02288247) presented at the 2022 Genitourinary Cancers Symposium.
The median PFS was 9.53 months (95% CI, 8.25-10.87) for those treated with enzalutamide vs 8.28 months (95% CI, 6.28-8.71) in the placebo arm (HR, 0.72; 95% CI, 0.53-0.96; P = .027). There was also delayed time to prostate specific antigen (PSA) progression at 8.44 months (95% CI, 8.18-9.00) in the enzalutamide group compared with 6.24 months (95% CI, 5.42-8.31) in the placebo group (HR, 0.58; 95% CI, 0.41-0.82; P = .002).
“These data suggest that continued treatment with enzalutamide plus docetaxel offers a clinical benefit and could be a future treatment option for some patients who progress on enzalutamide alone,” Axel S. Merseburger, MD, chairman of the Clinic of Urology at University Hospital Schleswig-Holstein in Lübeck, Germany, and lead investigator of the study, said during the presentation.
Investigators hypothesized that continuous treatment with enzalutamide may help maintain control of responsive tumor lesions and allow the addition of docetaxel to target pathways that enhance tumor growth.
A total of 273 patients were enrolled into the double-blind, open-label randomized trial, with 134 receiving treatment in the enzalutamide group and 135 in the placebo group. Patients received enzalutamide at 160 mg per day or matched placebo, docetaxel at 75 mg/m2 every 3 weeks, and prednisone at 10 mg every day. Treatment continued until disease progression.
Patient characteristics included median ages of 71.5 and 69.0 years for the enzalutamide and placebo groups, respectively, with median baseline PSA levels of 36.9 ng/mL vs 28.1 ng/mL. Most patients were White (97.8% vs 99.3%) and had a Gleason score of 8 or more (55.9% vs 57.0%). Location of metastasis was also similar between groups, with 41.9% in the enzalutamide group and 34.8% in the placebo group having bone lesions vs 21.3% and 17.8% with soft tissue metastases; 36.8% and 47.4%, respectively, had lesions at both sites.
The PFS by subgroup analysis showed consistent results to those from the overall population. Of note, no significant difference was noted for PFS outcomes in patients with baseline ECOG 0 (HR, 0.60; 95% CI, 0.45-1.06) or ECOG 1 (HR, 0.73; 95% CI, 0.48-1.15) status (P = .8404). Similar results were noted by disease location in bone only (HR, 1.14; 95% CI, 0.71-1.84), tissue only (HR, 0.42; 95% CI, 0.22-0.81), and both locations (HR, 0.53; 95% CI, 0.39-1.00; P = .0097).
There was a greater decrease in PSA from baseline to week 13 in the enzalutamide group at —37.12% compared with 9.11% in the placebo group.
The objective response rate via RECIST v1.1 was 31.6% (95% CI, 23.9%-40.1%) in the enzalutamide group and 25.9% (95% CI, 18.8%-34.2%) in the placebo group. Complete responses were observed in 26 patients (19.1%; 95% CI, 12.9%-26.7%) in the enzalutamide group vs 17 (12.6%; 95% CI, 7.5%-19.4%) in the placebo group. Partial responses were also seen in 17 (12.5%; 95% CI, 7.5%-19.3%) and 18 (13.3%; 95% CI, 8.1%-20.3%) patients, respectively.
Investigators found the safety profile to be consistent with known profile for this AR inhibitor. Serious treatment-emergent adverse effects (TEAEs) were seen in 49.3% of patients on enzalutamide vs 38.5% on placebo, and AEs leading to discontinuation occurred in 8.8% and 6.7%, respectively. Patients dying from any cause in the enzalutamide and placebo groups accounted for 9.6% and 5.2% of each respective population.
The most common TEAEs with enzalutamide vs placebo were asthenia (34.6% vs 25.9%), neutropenia (33.8% vs 33.3%), and alopecia (32.4% vs 27.4%). Median exposure to enzalutamide was 36.1 weeks vs 30.1 weeks with placebo.
Merseburger A, Attard G, Boysen G, et al. A randomized, double-blind, placebo (PBO)-controlled, phase 3b study of the efficacy and safety of continuing enzalutamide (ENZA) in chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with docetaxel (DOC) plus prednisolone (PDN) who have progressed on ENZA: PRESIDE. J Clin Oncol. 2022;40(suppl 6):15. doi: 10.1200/JCO.2022.40.6_suppl.015