medwireNews: The final analysis of the ARCHES trial has demonstrated a significant overall survival (OS) boost with the addition of enzalutamide instead of placebo to androgen deprivation therapy (ADT) in the metastatic castration-sensitive prostate cancer (mCSPC) setting.
These findings follow on from the primary analysis of the study showing a significant 61% reduction in the risk for radiographic disease progression with enzalutamide, and mirror those of the ENZAMET trial in which men with mCSPC were given either enzalutamide or a standard nonsteroidal anti-androgen (NSAA) alongside ADT.
As reported by Andrew Armstrong (Duke Cancer Institute, Durham, North Carolina, USA) at the ESMO Congress 2021, after a median 44.6 months of follow-up, the median OS duration was unreached for the 574 ARCHES participants who were randomly assigned to receive enzalutamide 160 mg/day together with ADT and the 576 who received placebo plus ADT. But the risk for death was 34% lower for those treated with the second-generation NSAA.
At the 2-year mark, 86% of men in the enzalutamide group were alive, as were 82% of those in the placebo group, while the 3- and 4-year OS rates were 78% versus 69% and 71% versus 57%, respectively.
Subgroup analysis showed that the OS benefit associated with enzalutamide use was maintained regardless of factors such as age, ECOG performance status, and baseline prostate-specific antigen levels, but further follow-up and analyses are needed to tease out the impact on men who have previously received docetaxel plus ADT and those with visceral metastases, said the presenter.
He highlighted that after the study unblinding crossover was permitted for placebo-treated patients who remained progression-free, and including crossover 42% of the men originally assigned to placebo ended up receiving enzalutamide, with 70% receiving any life-prolonging therapy after study treatment.
Enzalutamide treatment was also associated with a significant prolongation of median time to subsequent antineoplastic therapy relative to placebo, at unreached versus 40.5 months, and a reduction in the risk for use of antineoplastic therapy of 62%.
“Safety and toxicity data from this long-term final analysis are consistent with the initial primary results,” albeit with increases in some enzalutamide-related adverse events with longer follow-up, said Armstrong.
For instance, hypertension of grade 3–4 occurred in 5.1% of enzalutamide-treated participants, compared with 2.3% of those given placebo, with falls of this severity in 1.2% versus 0.5% and fractures in 3.5% versus 1.6%.
“These findings in conjunction with those of the primary ARCHES analysis support the net benefits of enzalutamide plus ADT in men with metastatic hormone-sensitive prostate cancer,” summarized Armstrong.
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