Continuation of enzalutamide in combination with docetaxel and androgen deprivation therapy (ADT) delays progression in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease previously progressed on enzalutamide, according to research published in The Lancet Oncology.
Patients who continued enzalutamide in combination with docetaxel and ADT had a median progression-free survival (PFS) of 9.5 months, which was significantly longer than the median PFS of 8.3 months observed in patients who received docetaxel and ADT in combination with placebo.
These results come from the phase 3b PRESIDE trial (ClinicalTrials.gov Identifier: NCT02288247). Period 1 of the trial included 688 patients with confirmed prostate adenocarcinoma and serum testosterone of 1.73 nmol/L or less who had progressed during ADT. During period 1, all patients received open-label enzalutamide at 160 mg daily.
Patients who had a decline in prostate-specific antigen (PSA) levels at week 13 and subsequently progressed were enrolled in period 2. These patients were treated with up to 10 cycles of docetaxel and oral prednisolone, and they were randomly assigned to receive oral enzalutamide (n=136) or placebo (n=135).
The median PFS was 9.5 months with enzalutamide and 8.3 months with placebo (hazard ratio [HR], 0.72; 95% CI, 0.53-0.96; P =.027). The median time to PSA progression was 8.4 months and 6.2 months, respectively (HR, 0.58; 95% CI, 0.41-0.82; P =.0021).
Rates of treatment-emergent adverse events (TEAEs) were similar between the treatment arms. Grade 3 TEAEs occurred in 38% of patients in the enzalutamide arm and 37% of those in the placebo arm. Grade 4 TEAEs occurred in 24% and 25%, respectively.
The most common grade 3 TEAEs (in the enzalutamide and placebo arms, respectively) were neutropenia (13% and 9%) and asthenia (7% and 4%). The most common grade 4 TEAE was neutropenia (17% and 21%).
Two of 13 deaths in the enzalutamide arm and 1 of 7 deaths in the placebo arm were associated with docetaxel. There were no deaths associated with the other study drugs.
“Although novel therapeutics are being studied to overcome enzalutamide resistance, our results suggest a potential subset of patients who might benefit from the treatment regimen tested in the current study. Continued studies will aim to pinpoint specific biomarkers of enzalutamide resistance to better identify the subsets of patients who will benefit the most from this innovative approach,” the researchers concluded.
Disclosures: This research was supported by Astellas Pharma and Pfizer. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Merseburger AS, Attard G, Åström L, et al. Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): An international, randomised, phase 3b study. Lancet Oncol. Published online October 17, 2022. doi:10.1016/S1470-2045(22)00560-5