This is a multi-center, randomized controlled trial of docetaxel + enzalutamide (DE) vs docetaxel alone (D) for first-line treatment of patients with mCRPC. Patients were randomized to receive docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg BID for a total of 8 cycles plus enzalutamide 160 mg daily and patients were stratified based on pain and visceral disease. The primary endpoint of the study was progression-free survival at 6 months after randomization.
246 patients were randomized to DE or D. Baseline characteristics were well balanced between both cohorts. The median age was 70 and most patients had an ECOG of 0-1. Most patients (78%) were asymptomatic and had no visceral metastases (74-78%).
In terms of the primary endpoint, 89.1% of patients receiving DE had no progression at 6 months compared with 72.8% of patients receiving D. PSA50 (decline in PSA by 50% from baseline) was also higher in the DE arm than the D arm (92.2% vs 70.0%; p < 0.0001). The median progression-free survival was significantly higher in the DE arm than the D arm, 11.3 months vs 9.1 months (p = 0.004) but overall survival was not found to be significantly different, 33.7 months vs 29.6 months.
In terms of safety, febrile neutropenia was observed in 10 patients on DE and 5 patients on D arm. Grade 3/4 anemia occurred in 3 patients on DE and 1 patient on D and grade 3/4 neutropenia occurred in 23 patients on DE and 19 patients on E.
This is the first randomized phase II study of docetaxel plus enzalutamide for patients with mCRPC. This trial demonstrates that combining docetaxel and enzalutamide upfront for patients with mCRPC increases median progression-free survival. However, there was no benefit seen for overall survival. Currently, other combinations are being explored with docetaxel, including Pembrolizumab + Docetaxel in Keynote 365. In addition to this combination being studied in the mCRPC space, the combination of the two therapies are currently being studied in the metastatic castration sensitive space with ENZADA.4
Presented By: Orazio Caffo, MD, Department of Medical Oncology, Santa Chiara Hospital, Italy
Written By: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA
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- Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. The New England Journal of Medicine 2014;371:424-33.
- Burgess EF, Grigg C, Clark PE, Boselli D, Symanowski JT, Raghavan D. A phase II trial of enzalutamide, docetaxel and androgen deprivation therapy (ENZADA) in patients with metastatic castrate-sensitive prostate cancer (mCSPC). American Society of Clinical Oncology; 2018.