The final overall survival (OS) analysis from the ARCHES trial published in the Journal of Clinical Oncology1 showed that adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) significantly improved overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
The final results from the phase 3 study showed that the addition of enzalutamide to ADT reduced the risk of death by 34% versus placebo plus ADT (median not reached in either group; hazard ratio [HR], 0.66; 95% CI, 0.53-0.81; P <.001). These data back the efficacy trend demonstrated in the primary analysis, which showed that adding enzalutamide to ADT significantly improved radiologic progression-free survival (rPFS).
Investigators in the phase 3 ARCHES trial (NCT02677896) enrolled 1150 patients with mHSPC and randomized them 1:1 to receive 160 mg of enzalutamide once daily plus ADT or to receive placebo plus ADT. Patients were stratified by disease volume and prior docetaxel (Taxotere) use. After the preliminary analysis, the study was unblinded to allow those who were randomly assigned to the placebo group to cross over to the enzalutamide group in an open-label extension. Key secondary end points reported in this updated analysis are overall survival (OS), defined time from random assignment to death from any cause, and rPFS.
Investigators reported 154 deaths among the 574 patients who were randomly assigned to enzalutamide plus ADT compared with 202 deaths of the 576 patients who were randomly assigned to placebo plus ADT.
After ARCHES unblinded, 184 patients (31.9%) in the placebo plus ADT arm remained progression-free and consented to cross over. Among those who crossed over, 180 of these patients (31.3%) received treatment with enzalutamide plus ADT, with a median time to crossover of 21.5 months. After 356 deaths, the data cutoff for the final OS analysis with a median follow-up time of 44.6 months.
After treatment discontinuation, 131 patients (23%) in the enzalutamide plus ADT group and 221 patients (38%) in the to placebo plus ADT group received subsequent life-prolonging therapy. Including patients who crossed over, 401 patients (70%) randomly assigned to placebo plus ADT received subsequent life-prolonging therapy.
The enzalutamide plus ADT group experienced a delayed time to first subsequent antineoplastic therapy of which the median was not reached vs 40.5 months for placebo plus ADT (HR, 0.38; 95% CI, 0.31-0.48). The treatment of enzalutamide plus ADT reduced the risk of radiographic progression or death by 37%, extending the median rPFS by approximately 11 months compared with treatment with placebo plus ADT. Prostate specific antigen progression was found in117 patients (20%) in the enzalutamide plus ADT group compared with 259 (45%) in the placebo plus ADT group.
The median age of patients in the enzalutamide group was 70.0 years (range, 46-92), 70.0 years (range, 42-92) in the placebo group, and 69.0 years (range, 51-89) in those who crossed over from the placebo group. More than 75% of all patients were white. Patients had ECOG performance scores of either 0 or 1, with patients in the enzalutamide group, placebo group, and crossover group scoring 0 in 78.0%, 76.9%, and 84.2%, respectively. Visceral disease was observed in 11% of patients in both enzalutamide and placebo groups as well as 9.4% of patients in the crossover group. A small portion of patients received no previous ADT (6.8% in the enzalutamide group; 10.6% in the placebo group; 11.4% in the crossover group).
The median treatment duration was 40.2 months for the enzalutamide group, 13.8 months for the placebo group, and 23.9 months in the crossover group. Investigators noted the occurrence of treatment-emergent adverse events was consistent with the primary analysis, and no new safety signals were identified.
Previously reported efficacy benefits with enzalutamide plus ADT vs placebo plus ADT remain and are further confirmed with additional follow up. Along with no new emerging safety signals, these data indicate that longer-term use of enzalutamide was well tolerated and not associated with any new toxicity concerns.
1. Armstrong AJ, Azad AA, Iguchi T, et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer [published online ahead of print April 14, 2022]. J Clin Oncol. 2022. doi: 10.1200/JCO.22.00193.