Continuous treatment with the androgen receptor inhibitor enzalutamide, in combination with docetaxel, significantly improved progression-free survival (PFS) compared with placebo plus docetaxel in men with metastatic castration-resistant prostate cancer whose disease progressed while receiving enzalutamide alone in the phase 3b PRESIDE clinical trial. Axel S. Merseburger, MD, PhD, Clinic of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany, reported the results at the 2022 ASCO GU Cancers Symposium.
The investigators hypothesized that continuous treatment with enzalutamide may help maintain control of responsive tumor lesions and may allow the addition of docetaxel to target pathways that enhance tumor growth.
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 had no evidence of radiographic progression were not eligible for period 2, during which 273 patients remained and were randomized (1:1) to enzalutamide 160 mg daily, or to placebo. All patients also received docetaxel 75 mg/m2 every 3 weeks, and prednisone 10 mg daily. Treatment continued until disease progression.
The median patient ages were 71.5 years and 69 years for the enzalutamide and placebo arms, respectively. The median baseline PSA levels were 36.9 ng/mL and 28.1 ng/mL, respectively. The majority of the patients were white (97.8% and 99.3%, respectively), and 55.9% and 57% of the patients had a Gleason score of ≥8, respectively. Bone lesions were present in 41.9% of the patients in the enzalutamide arm and in 34.8% of the placebo arm, soft-tissue metastases in 21.3% and 17.8%, respectively, and lesions at both sites were present in 36.8% and 47.4% of the patients, respectively.
The median PFS was 9.53 months with enzalutamide plus docetaxel versus 8.28 months with placebo plus docetaxel (hazard ratio, 0.72; P = .027). In addition, 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 in PFS was seen between the patients with a baseline ECOG performance score of 0 and 1. The PFS was also similar by disease location in bone only, tissue only, and in both locations (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 based on RECIST version 1.1 was 31.6% in the enzalutamide arm and 25.9% in the placebo arm, with complete response rates of 19.1% and 12.6%, respectively.
“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,” said Dr Merseburger.
The safety profile of enzalutamide was consistent with its known profile. Serious treatment-emergent adverse events were observed in 49.3% of patients who received enzalutamide versus 38.5% of the patients who received placebo. Adverse events leading to treatment discontinuation occurred in 8.8% and 6.7% of the patients, respectively, and 9.6% and 5.2% of the patients, respectively, died from any cause.
Based on these results, patients whose disease responds initially to treatment with enzalutamide, but who ultimately have disease progression within 15 months; those with ongoing clinical benefit from enzalutamide; and those who demonstrate fitness for combination therapy should be considered for continuous enzalutamide combination therapy, said Elisabeth I. Heath, MD, FACP, Hartmann Endowed Chair for Prostate Cancer Research, Karmanos Cancer Institute, Detroit, MI.
“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,” Dr Heath said.