Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature. In the phase III, double-blind, global ARCHES trial (ClinicalTrials.gov identifier: NCT02677896 ), 1,150 patients with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg once daily) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use. Here, we report the final prespecified analysis of overall survival (key secondary end point) and an update on rPFS, other secondary end points, and safety. After unblinding, 180 (31.3%) progression-free patients randomly assigned to placebo plus ADT crossed over to open-label enzalutamide plus ADT. As of May 28, 2021 (median follow-up, 44.6 months), 154 of 574 patients randomly assigned to enzalutamide plus ADT and 202 of 576 patients randomly assigned to placebo plus ADT had died. Enzalutamide plus ADT reduced risk of death by 34% versus placebo plus ADT (median not reached in either group; hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P < .001). Enzalutamide plus ADT continued to improve rPFS and other secondary end points. Adverse events were generally consistent with previous reports of long-term enzalutamide use. In conclusion, enzalutamide plus ADT significantly prolongs survival versus placebo plus ADT in patients with mHSPC.

Addition of Docetaxel to Androgen Receptor Axis–targeted Therapy and Androgen Deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer: A Network Meta-analysis

“…abstracts and a yet to be indexed article [12,[24][25][26], and three abstracts with updated analyses [11,27,28] of included RCTs. During the peer review process for this article in April 2022, full-text publications of two RCTs [29,30] and an update to a third RCT [31] appeared. These publications were included but did not alter the analysis that was based on identical abstract data presented previously.…”

“…[1,2,5,6,[8][9][10][11][12][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Overall, across these 11 RCTs, 11 546 patients were treated in one of the four treatment regimens: ADT alone (n = 4548), ADT plus ARAT (n = 3211), ADT plus docetaxel (n = 2366), and the triplet of ADT, ARAT, and docetaxel (n = 1421).…”

Reply to R. Sun et al

“…We recently published results from the final prespecified analysis of overall survival (OS) in the ARCHES trial, a phase III, double-blind study of enzalutamide (160 mg once daily) plus androgen deprivation therapy (ADT) versus placebo plus ADT. 1 In that analysis, enzalutamide plus ADT demonstrated a clinically meaningful and statistically significant increase in OS compared with placebo plus ADT (hazard ratio [HR], 0.66; 95% CI, 0.53 to 0.81; log-rank P , .001).…”

Introducing Clinical Trial Updates

“…In the article that accompanies this editorial, Armstrong et al 2 demonstrate that the addition of enzalutamide reduced the risk of death by 34% compared with androgen deprivation therapy alone in men with metastatic hormone-sensitive prostate cancer, despite cross over in nearly one third of patients. This report debuts a new article type for the Journal of Clinical Oncology , the Clinical Trial Update, which provides a rigorous short form to disseminate impactful updated results of previously reported clinical trials.…”

“…Specially, they argued that OS might be maintained with enzalutamide used at the time of progression on ADT, limiting toxicity and cost during initial therapy. In the article that accompanies this editorial, Armstrong et al 2 address those questions. Now with an additional 30-month follow-up, the addition of enzalutamide reduced the risk of death by 34% compared with ADT alone (hazard ratio = 0.66; P < .001), despite cross over in nearly one third of patients.…”