As reported in The Lancet Oncology by Christopher J. Sweeney, MBBS, and colleagues, the primary overall survival analysis of the phase III ENZAMET trial showed a significant benefit with enzalutamide plus testosterone suppression vs standard nonsteroidal antiandrogen treatment plus testosterone suppression in patients with metastatic hormone-sensitive prostate cancer.
Christopher J. Sweeney, MBBS
Study Details
In the international open-label trial, 1,125 patients were randomly assigned between March 2014 and March 2017 to receive testosterone suppression plus enzalutamide at 160 mg once per day (n = 563) or testosterone suppression plus nonsteroidal antiandrogen treatment with bicalutamide, nilutamide, or flutamide (control group; n = 562), with treatment continued until clinical progression or prohibitive toxicity. Testosterone suppression was allowed up to 12 weeks before random assignment and for up to 24 months as adjuvant therapy. Concurrent docetaxel at 75 mg/m² was allowed for up to six cycles every 3 weeks at patient and physician discretion. The primary endpoint was overall survival in the intention-to-treat population.
At the first interim analysis of overall survival, after a median follow-up of 34 months, patients in the enzalutamide group showed a significant benefit (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.52–0.86, P = .002); the analysis did not show a clear benefit of adding concurrent docetaxel to enzalutamide.
Key Findings
Median follow-up was 68 months (interquartile range = 67–69 months). A total of 164 (61%) of 268 patients who had disease progression in the enzalutamide group and 353 (85%) of 413 patients with disease progression in the control group received further active therapy at data cutoff. Median overall survival was not reached in the enzalutamide group or in the control group (HR = 0.70, 95% CI = 0.58–0.84, P < .0001), with 5-year overall survival of 67% (95% CI = 63%–70%) in the enzalutamide group vs 57% (95% CI = 53%–61%) in the control group.
Median prostate-specific antigen progression-free survival was 68.0 months in the enzalutamide group vs 22.0 months in the control group (HR = 0.44, 95% CI = 0.38–0.52). Median clinical progression–free survival was 81.0 months in the enzalutamide group vs 25.0 months in the control group (HR = 0.45, 95% CI = 0.39–0.53).
In subgroup analyses, hazard ratios for overall survival for the enzalutamide group vs the control group were: 0.54 (95% CI = 0.39–0.74) for low-volume disease and 0.79 (95% CI = 0.63–0.98) for high-volume disease; and 0.82 (95% CI = 0.63–1.06) for planned docetaxel use and 0.60 (95% CI = 0.47–0.78) for no planned docetaxel use. Among patients with synchronous metastatic disease who were treated with docetaxel, the hazard ratio was 0.73 (95% CI = 0.55–0.99). Among patients with metachronous metastatic disease who received docetaxel, the hazard ratio was 1.10 (95% CI = 0.65–1.86).
Updated adverse event profiles showed that the most common grade 3 or 4 adverse events were febrile neutropenia associated with docetaxel (6% of patients the enzalutamide group vs 6% of those in the control group), fatigue (6% vs 1%), and hypertension (10% vs 6%). The incidence of grade 1 to 3 memory impairment was 13% vs 4%. No deaths were considered related to study treatment.
The investigators concluded, “The addition of enzalutamide to standard of care showed sustained improvement in overall survival for patients with metastatic hormone-sensitive prostate cancer and should be considered as a treatment option for eligible patients.”
Dr. Sweeney, of the South Australian Immunogenomics Cancer Institute, University of Adelaide, Australia, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Astellas Pharma. For full disclosures of the study authors, visit thelancet.com.
