Study details
Men enrolled in ARCHES were allowed to have received prior ADT for up to 3 months or, if they had received docetaxel, for up to 6 months, Dr. Armstrong noted at the symposium.
About two-thirds each had high disease volume and had distant metastasis at their initial diagnosis. Overall, median duration of prior ADT was 1.6 months.
Radiographic progression-free survival was not reached with enzalutamide versus 19.45 months with placebo (hazard ratio, 0.39; P less than .0001). Corresponding 12-month rates were 84% and 64%. Findings were essentially the same across diverse subgroups, including among the 18% of patients who had received prior docetaxel (HR, 0.53).
Median time to PSA progression – typically one of the first indications of castration resistance – was not reached in either group, but the 12-month rate was 91% with enzalutamide versus 63% with placebo (HR, 0.19; P less than .0001), Dr. Armstrong reported. Median time to castration resistance was not reached with enzalutamide versus 13.9 months with placebo (HR, 0.28; P less than .0001).
There also were significant differences in favor of enzalutamide on the rate of achievement of undetectable PSA (68.1% vs. 17.6%; P less than .0001), the objective response rate (83.1% vs. 63.7%; P less than .0001), and the time to initiation of new antineoplastic therapy (not reached vs. 30.19 months; HR, 0.28; P less than .0001).
Quality of life was very high in both groups at study baseline and remained similarly so during follow-up. An interim analysis showed overall survival had not been reached in either group, although there was a nonsignificant trend favoring enzalutamide.
Safety was much the same, with the enzalutamide and placebo groups having similar rates of grade 3 or worse adverse events (24.3% vs. 25.6%), as well as similar rates of adverse events leading to treatment withdrawal (7.2% vs. 5.2%) and death (2.4% vs. 1.7%).
In terms of adverse events of special interest, the groups were comparable on rates of grade 3 or 4 convulsion, ischemic heart disease, falls, and fractures.
Dr. Armstrong disclosed that he has a consulting or advisory role with, receives research funding (institutional) from, and receives travel, accommodations, and/or expenses from Astellas – among other disclosures. The trial was sponsored by Astellas.
SOURCE: Armstrong AJ et al. GUCS 2019, Abstract 687.