In the European phase IIIb PRESIDE trial reported in The Lancet Oncology, Merseburger et al found that treatment with docetaxel and continuing enzalutamide vs placebo improved progression-free survival in patients with metastatic castration-resistant prostate cancer who had disease progression on enzalutamide.
The two-period trial enrolled patients progressing on androgen-deprivation therapy (ADT) at sites in 16 European countries between December 2014 and February 2016.
In part 1 of the study, 687 patients received open-label enzalutamide at 160 mg/d with continued ADT. At week 13, patients were evaluated for radiographic or prostate-specific antigen (PSA) progression (25% or more increase and ≥ 2 ng/mL above nadir); those with any decline in PSA at week 13 who subsequently had disease progression (radiographic progression, PSA progression, or both) were enrolled in part 2. In part 2, patients received up to 10 cycles of docetaxel at 75 mg/m² every 3 weeks and prednisolone at 10 mg/d and were randomly assigned in double-blind fashion to continue enzalutamide at 160 mg/d or receive placebo with ongoing ADT.
The primary endpoint was progression-free survival in part 2 (excluding PSA progression).
In part 2, 271 patients were randomly assigned to receive enzalutamide (n = 136) or placebo (n = 135). Median follow-up in part 2 was 8.1 months (interquartile range [IQR] = 3.2–11.1 months) in the enzalutamide group and 6.3 months (IQR = 3.1–10.5 months) in the placebo group. Median progression-free survival was 9.5 months (95% confidence interval [CI] = 8.3–10.9 months) in the enzalutamide group vs 8.3 months (95% CI = 6.3–8.7 months) in the placebo group (hazard ratio [HR] = 0.72, 95% CI = 0.53–0.96, P = .027).
Median time to PSA progression was 8.4 months (95% CI = 8.2–9.0 months) in the enzalutamide group vs 6.2 months (95% CI = 5.4–8.3 months) in the placebo group (HR = 0.58, 95% CI = 0.41–0.82, P = .0021). Median time to first skeletal-related event was 22.0 months (95% CI = 15.2 months to not evaluable) in the enzalutamide group vs 17.4 months (95% CI = 17.4 months to not evaluable) in the placebo group (HR = 1.00, 95% CI = 0.47–2.13, P = .99).
In part 2, grade 3 adverse events occurred in 38% of patients in the enzalutamide group vs 37% of the placebo group, most commonly neutropenia (13% vs 9%); adverse events were considered related to docetaxel in 32% vs 28% of patients. Grade 4 adverse events occurred in 24% vs 25% of patients, most commonly neutropenia (17% vs 21%); adverse events were considered related to docetaxel in 24% vs 25% of patients.
Serious adverse events occurred in 49% vs 39% of patients. Adverse events led to treatment discontinuation in 9% vs 7%. Two deaths in the enzalutamide group and one in the placebo group were considered related to docetaxel; no deaths were considered related to enzalutamide or placebo.
The investigators concluded, “PRESIDE met its primary endpoint and showed that continuing enzalutamide with docetaxel plus ADT delayed time to progression compared with docetaxel plus ADT alone, supporting the hypothesis that enzalutamide maintenance could control persistent androgen-dependent clones in [patients with] metastatic castration-resistant prostate cancer [whose disease progresses] after treatment with enzalutamide alone.”
Axel S. Merseburger, MD, of Universitätsklinikum Schleswig-Holstein, Lübeck, Germany, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Astellas Pharma and Pfizer. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.