Continuing Enzalutamide After Progression Improves PFS in Metastatic Castration Resistant Prostate Cancer: PRESIDE Study

In a phase 3 study, continuous enzalutamide with docetaxel plus androgen deprivation therapy (ADT) delayed time to progression for patients with metastatic castration-resistant prostate cancer, compared to docetaxel plus ADT alone. As lead investigator Axel Merseburger, MD, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany, and coauthors, wrote, “Although androgen deprivation therapy is typically given long-term for men with metastatic prostate cancer, second-generation hormone therapies are generally discontinued before the subsequent line of treatment.”

The multinational, double-blind, phase 3b PRESIDE study, was a 2-period study. Period 1 enrolled 687 patients with prostate adenocarcinoma who had progressed during ADT. Patients received 160 mg enzalutamide orally once per day. Those patients who showed decline in prostate-specific antigen (PSA) at week 13 and subsequently progressed were enrolled in Period 2 of the study.

In Period 2, a total of 271 patients were randomly assigned on a 1:1 basis to receive up to 10 cycles of intravenous docetaxel every 3 weeks with 10 mg per day of oral prednisolone plus either 10 mg/day enzalutamide orally (n = 136), or placebo (n = 135). The primary end point of the study was progression-free survival (PFS) of all patients in Period 2.

The median PFS of the enzalutamide group was 9.5 months (95% confidence interval [CI], 8.3 to 10.9), compared to 8.3 months (95% CI, 6.3 to 8.7) in the placebo group (hazard ratio, 0.72; 95% CI, 0.53 to 0.96; P = .027).

The most common grade 3 treatment-emergent adverse events were neutropenia (13% in the enzalutamide group vs 9% in the placebo group) and asthenia (7% vs 4%). In Period 2, the most common grade 4 treatment-emergent adverse event was neutropenia, occurring in 17% of the enzalutamide group and 21% of the placebo group. In the enzalutamide group, 49% of patients reported serious treatment-emergent adverse events, compared to 39% in the placebo group.

Of 13 deaths in the enzalutamide group, 2 (caused by septic shock and hematuria) were associated with docetaxel, compared to 1 (caused by acute kidney injury) of 7 deaths in the placebo group.

Dr Merseburger and colleagues concluded, “PRESIDE met its primary endpoint…, supporting the hypothesis that enzalutamide maintenance could control persistent and androgen-dependent clones in men with [metastatic castration-resistant prostate cancer] who progress after treatment with enzalutamide alone.”

Source:

Merseburger A, Attard G, Åström, et al. Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetazel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol. Published online October 17, 2022. doi:10.1016/S1470-2045(22)00560-5