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Level-1 evidence indicates that adding docetaxel, abiraterone, or apalutamide to standard androgen-deprivation therapy (ADT) can improve overall survival (OS) in many men with hormone-sensitive metastatic prostate cancer (HSMPC).
Now, international investigators have conducted an industry-funded, open-label, randomized, phase III study involving 1125 men with HSMPC (median age, 69 years) to compare the value of adding a next-generation androgen-receptor inhibitor (enzalutamide) to ADT versus adding a first-generation androgen-receptor inhibitor (bicalutamide, nilutamide, or flutamide) to ADT (control group). The protocol was modified after enrollment of 88 patients to allow patients to have previously received docetaxel for HSMPC.
At a median follow-up of 34 months, 3-year OS (the primary endpoint) was significantly longer in the enzalutamide group than in the control group (80% vs. 72%; hazard ratio, 0.67; P=0.002), as were prostate-specific antigen (PSA) progression-free survival (PFS) and clinical PFS. These results were not affected by volume of disease or prior use of docetaxel. At 3 years, the percentage of patients still receiving a trial regimen was 62% in the enzalutamide group and 34% in the control group. Fatigue and seizures were more common with enzalutamide.
Davis ID et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 2019 Jun 2; [e-pub]. (https://doi.org/10.1056/NEJMoa1903835)
Comment
In this well-conducted study, the benefit of enzalutamide on OS was not affected by prior receipt of docetaxel or subsequent therapies. The authors note that the effect of enzalutamide on OS appeared smaller in the subgroup receiving prior docetaxel, but that the study was not powered to address this issue. There is a therapy burden associated with enzalutamide that must be considered by clinicians and patients as they review the evolving treatment options in this clinical space. Longer follow-up of this trial will likely provide important information.