EMBARK (enzalutamide monotherapy)
Trial question
What is the role of enzalutamide monotherapy in patients with prostate cancer with high-risk biochemical recurrence?
Study design
Multi-center
Open label
RCT
Population
713 male patients.
Inclusion criteria: prostate cancer who had high-risk biochemical recurrence with a PSA doubling time ≤ 9 months.
Key exclusion criteria: distant metastatic disease; prior hormonal, cytotoxic, or biologic therapy; major surgery within 4 weeks before randomization.
Interventions
N=355 enzalutamide monotherapy (enzalutamide at an oral dose of 160 mg/day).
N=358 leuprolide alone (leuprolide at a dose of 22.5 mg IV or SC every 12 weeks).
Primary outcome
Metastasis-free survival at 5 years
80%
71.4%
80.0 %
60.0 %
40.0 %
20.0 %
0.0 %
Enzalutamide
monotherapy
Leuprolide
alone
Significant
increase ▲
NNT = 11
Significant increase in metastasis-free survival at 5 years (80% vs. 71.4%; HR 1.59, 95% CI 1.15 to 2.17).
Secondary outcomes
Significant increase in free from PSA progression at 5 years (88.9% vs. 70%; HR 3.03, 95% CI 2.04 to 4.35).
Significant increase in free from antineoplastic therapy at 5 years (75.7% vs. 61.7%; HR 1.85, 95% CI 1.41 to 2.44).
No significant difference in overall survival at 5 years (89.5% vs. 87.2%; HR 1.28, 95% CI 0.85 to 1.92).
Safety outcomes
No significant difference in adverse event.
Conclusion
In prostate cancer who had high-risk biochemical recurrence with a PSA doubling time ≤ 9 months, enzalutamide monotherapy was superior to leuprolide alone with respect to a metastasis-free survival at 5 years.
Reference
Stephen J Freedland, Murilo de Almeida Luz, Ugo De Giorgi et al. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465.
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