Apalutamide for Metastatic Castration-Sensitive Prostate Cancer
abstract
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Access this abstract nowBackground
Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression–free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.
Methods
In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression–free survival and overall survival.
Results
A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression–free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.
Conclusions
In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression–free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups.
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Additional Info
Disclosure statements are available on the authors' profiles:
Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer
N. Engl. J. Med 2019 May 31;[EPub Ahead of Print], KN Chi, N Agarwal, A Bjartell, et alAdvanced Prostate Cancer Center of Excellence
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Apalutamide has been FDA-approved in the context of nonmetastatic castrate-resistant disease. This is the first study in the context of metastatic castration-sensitive prostate cancer, and it has a very simple trial design with ADT plus or minus apalutamide at 240 mg a day, and there was prior docetaxel allowed. There was the possibility of using docetaxel, but this was only present in a minority of individuals. The patients were a median of 68 years old, and about 10% had previous docetaxel therapy. There was an unequivocal improvement in both overall survival and progression-free survival. The hazard ratio for death was 0.67, meaning a 33% reduction in the risk of death.
The apalutamide was well-tolerated as a whole, although rashes and hypothyroidism were noted, as was consistent with previous apalutamide trials, and this will become a new standard of care. This apalutamide trial needs to be viewed in the context of the previous abiraterone trials, particularly, LATITUDE and STAMPEDE, or the LATITUDE trials and the ENZAMET trial, which will be discussed in this same group of articles.