Continuous Enzalutamide Reduces Risk for Progression in Patients with Metastatic Castration-Resistant Prostate Cancer

TON - April 2022 Vol 15, No 2

Continuous enzalutamide (Xtandi) treatment in combination with docetaxel significantly improved progression-free survival (PFS) compared with placebo plus docetaxel in men with metastatic castration-resistant prostate cancer who had disease progression on enzalutamide alone, according to results from the phase 3b PRESIDE clinical trial. Median PFS was 9.53 months for patients randomized to enzalutamide versus 8.28 months for those in the placebo arm (hazard ratio [HR], 0.72; P = .027), reported lead investigator Axel S. Merseburger, MD, PhD, Chairman, Clinic of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany, at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium.

“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,” he said during the presentation.

Dr Merseburger and colleagues 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.

Study Details

The double-blind, open-label, randomized PRESIDE study enrolled 687 patients in period 1, when open-label enzalutamide was given. Patients who had no prostate-specific antigen (PSA) response or who were primary resistant were not eligible for period 2, during which 273 remaining patients were randomly assigned in a 1:1 ratio to receive enzalutamide (N = 134) or placebo (N = 135). All patients received docetaxel and prednisone. Enzalutamide was given at 160 mg daily, docetaxel at 75 mg/m2 every 3 weeks, and prednisone at 10 mg daily. Treatment was continued until disease progression.

Median patient age was 71.5 years and 69.0 years for the enzalutamide and placebo arms, respectively. The median baseline PSA levels were 36.9 ng/mL in patients receiving enzalutamide and 28.1 ng/mL in those receiving placebo. Some 97.8% and 99.3% in each arm were white, and 55.9% versus 57.0% had a Gleason score ≥8, respectively. Bone lesions were present in 41.9% of the enzalutamide arm and 34.8% of the placebo arm, soft tissue metastases in 21.3% and 17.8%, respectively, and lesions at both sites in 36.8% and 47.4%, respectively.

In addition to improving PFS, enzalutamide treatment delayed the time to PSA progression (8.4 months vs 6.2 months with placebo).

The PFS by subgroup analysis was consistent with results from the overall study population. No significant difference was observed in PFS in patients with baseline Eastern Cooperative Oncology Group performance status 0 (HR, 0.60; 95% confidence interval [CI], 0.45-1.06) or Eastern Cooperative Oncology Group performance status 1 (HR, 0.73; 95% CI, 0.48-1.15; P = .8404). Likewise, PFS was similar 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 in both locations (HR, 0.53; 95% CI, 0.39-1.00; P = .0097).

The PSA level decreased by 37.12% from baseline to week 13 in the enzalutamide arm compared with 9.11% in the placebo arm.

The objective response rate via RECIST version 1.1 was 31.6% in the enzalutamide arm and 25.9% in the placebo arm, with a complete response rate of 19.1% and 12.6%, respectively.

The safety profile of enzalutamide was consistent with the known profile for this androgen receptor inhibitor. Serious treatment-emergent adverse effects were observed in 49.3% of patients assigned to enzalutamide versus 38.5% of those assigned to placebo. Adverse events leading to discontinuation occurred in 8.8% and 6.7%, respectively, and 9.6% and 5.2%, respectively, died from any cause.

Expert Commentary

According to discussant Elisabeth I. Heath, MD, FRCP, Associate Director, Translational Science, and Professor, Hematology-Oncology, Karmanos Cancer Institute, Hudson-Webber Cancer Research Center, Detroit, MI, patients to consider for continuous enzalutamide combination therapy, based on the results from PRESIDE, are those whose disease responds initially to enzalutamide, but who ultimately have disease progression within 15 months; those with ongoing clinical benefit from enzalutamide; and those with demonstrated fitness for combination therapy.

“The addition of docetaxel in men who are progressing on enzalutamide is a treatment option due to an increase in PFS in men with metastatic castration-resistant prostate cancer,” she said.

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