In patients with metastatic castration-resistant prostate cancer (CRPC) who have progressed on enzalutamide (Xtandi), those who continued the treatment in combination with docetaxel and prednisolone saw improved progression-free survival (PFS), the phase IIIb PRESIDE study found.

Median PFS was 9.53 months with the the enzalutamide-based combination compared with 8.28 months in those treated with placebo and docetaxel plus prednisolone (HR 0.72, 95% CI 0.53-0.96, P=0.027), reported Axel S. Merseburger, MD, PhD, of University Hospital Schleswig-Holstein in Lübeck, Germany, during his presentation at the Genitourinary Cancers Symposium.

This combination provides another treatment option for men with metastatic CRPC who have progressed on enzalutamide, noted discussant Elisabeth Heath, MD, of Karmanos Cancer Institute at Wayne State University School of Medicine in Detroit.

“From a patient perspective, a PFS endpoint has meaning, and can have clinical benefit, as long as the safety is there,” she said. “It is important to recognize that the additional medication does not really worsen the toxicity.”

As for secondary endpoints, median time to prostate-specific antigen (PSA) progression was 8.44 months with enzalutamide versus 6.24 months with placebo (HR 0.58, 95% CI 0.41-0.82, P=0.002). There was also a greater mean decrease in PSA levels from baseline in the enzalutamide group (-37.12%) compared with the placebo group (9.11%) at week 13.

The overall response rate was 31.6% in the enzalutamide group versus 25.9% in the placebo group. Complete response rates were 19.1% and 12.6%, respectively.

The safety profile of the combination was acceptable and consistent with the known individual safety profiles of the drugs, Merseburger said.

The open-label first period of PRESIDE included 687 patients with metastatic CRPC who were treated with enzalutamide 160 mg daily. After 13 weeks, 271 patients with a PSA response of ≥50% change from baseline and later progression were eligible for the trial’s second period, in which they were randomized 1:1 to enzalutamide or placebo plus docetaxel and prednisolone.

PFS subgroup analyses demonstrated consistent benefits with the overall population, Merseburger noted. The largest PFS benefits were observed in the subgroups with disease confined to the tissue (HR 0.42, 95% CI 0.22-0.81) and those with disease located in the bone and tissue (HR 0.63, 95% CI 0.39-1.00), as well as those with visceral disease (HR 0.29, 95% CI 0.10-0.85), “suggesting that those aggressive tumors may benefit from this therapy intensification in metastatic CRPC,” he said.

Serious treatment-emergent adverse events (TEAEs) were reported in 49.3% of patients in the enzalutamide group and 38.5% of patients in the placebo group, with TEAEs leading to permanent treatment discontinuation in 8.8% and 6.7%, respectively. There were 13 deaths (9.6%) in the enzalutamide group and seven deaths (5.2%) in the placebo group.

The most common TEAEs were asthenia (34.6% of the enzalutamide group vs 25.9% of the placebo group), neutropenia (33.8% vs 33.3%), and alopecia (32.4% vs 27.4%).

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