Undetectable PSA Levels Tied to Improvements in rPFS, OS in Metastatic Hormone-Sensitive Prostate Cancer

Patients with metastatic hormone-sensitive prostate cancer (mHSPC) who receive enzalutamide plus androgen deprivation therapy (ADT) are 4 times more likely to achieve undetectable prostate-specific antigen (PSA) levels than patients who receive ADT alone, according to a post hoc analysis of the ARCHES trial.¹

The analysis also showed that patients with undetectable PSA levels had better radiographic progression-free survival (rPFS) and overall survival (OS) than patients with detectable PSA levels.

These results were presented in a poster at JADPRO Live 2022, the annual APSHO meeting.

The ARCHES trial (ClinicalTrials.gov Identifier: NCT02677896) included 1150 patients with mHSPC. They were randomly assigned to receive enzalutamide plus ADT (n=574) or placebo plus ADT (n=576). Crossover was allowed.

Prior results showed that adding enzalutamide to ADT significantly improved rPFS and OS.² For this post hoc analysis, researchers assessed clinical endpoints in patients who reached undetectable PSA levels (<0.2 ng/mL) on either treatment and investigated predictors of PSA decline.¹

A total of 348 patients (68.6%) in the enzalutamide-ADT arm and 89 (17.6%) in the placebo-ADT arm reached undetectable PSA levels.

Patients in both treatment arms had superior rPFS and OS if they had undetectable PSA levels. In the enzalutamide arm, the hazard ratio (HR) for rPFS was 0.14 (95% CI, 0.09-0.23), and the HR for OS was 0.24 (95% CI, 0.17-0.34). In the placebo arm, the HR for rPFS was 0.24 (95% CI, 0.13-0.43), and the HR for OS was 0.35 (95% CI, 0.22-0.57).

Patients with undetectable PSA levels also had improvements in:

• Time to PSA progression (enzalutamide HR, 0.05; 95% CI, 0.02-0.12; placebo HR, 0.07; 95% CI, 0.02-0.17)
• Time to new antineoplastic therapy (enzalutamide HR, 0.13; 95% CI, 0.06-0.26; placebo HR, 0.12; 95% CI, 0.05-0.33)
• Time to castration resistance (enzalutamide HR, 0.16; 95% CI, 0.10-0.25; placebo HR, 0.16; 95% CI, 0.09-0.29)
• Time to symptomatic skeletal events (enzalutamide HR, 0.40; 95% CI, 0.19-0.83; placebo HR, 0.16; 95% CI, 0.04-0.66).

In both treatment arms, patients with undetectable PSA levels had more treatment-emergent adverse events (TEAEs) than patients with detectable PSA levels — 86.3% and 83.8%, respectively. However, the rate of grade 3-4 TEAEs was lower in patients with undetectable PSA levels (21.3% vs 26.3%).

A multivariate analysis suggested that potential predictors for achieving undetectable PSA levels with enzalutamide plus ADT are the absence of de novo disease at diagnosis (odds ratio [OR], 4.3; 95% CI, 1.8-10.6; P =.001) and a baseline PSA level of 7.2 ng/mL or lower (OR, 3.3; 95% CI, 2.1-5.2; P <.0001).

Disclosures: This research was funded by Pfizer, Inc. and Astellas Pharma, Inc. The study authors disclosed affiliations with Pfizer, Astellas, and many other companies.

References

1. Stenzi A, Shore ND, Villers A, et al. Clinical outcomes of patients with metastatic hormone-sensitive prostate cancer (mHSPC) with prostate-specific antigen (PSA) decline to undetectable levels on enzalutamide (ENZA): Post hoc analysis of ARCHES. Poster presented at: JADPRO Live 2022; October 20-23, 2022; Aurora, CO. Abstract JL1004E.
2. Armstrong AJ, Iguchi T, Azad AA, et al. Final overall survival (OS) analysis from ARCHES: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC). ESMO 2021; September 16-21, 2021. Abstract LBA25.