JL1004E: 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

Introduction & objectives:
In the previously reported ARCHES trial (NCT02677896), ENZA + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT improved overall survival (OS) and clinical outcomes in men with mHSPC. This post hoc analysis assessed clinical endpoints in men with mHSPC who reached undetectable PSA levels on ENZA+ADT or PBO+ADT and investigated predictors of such a PSA decline.

Materials & methods:
Men with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO+ADT, stratified by disease volume and prior docetaxel. Post hoc analyses were based on reaching undetectable ( < 0.2 ng/mL) or detectable (≥0.2 ng/mL) PSA levels during study treatment and included men with both detectable baseline PSA (≥0.2 ng/mL) and postbaseline PSA measurements (ENZA+ADT, n=507; PBO+ADT, n=504). Stepwise multivariate analysis was conducted on variables from a univariate logistic regression model to identify clinical factors that significantly correlated with PSA decline to undetectable levels.

Results:
PSA undetectable groups had fewer men with high-volume disease, Gleason scores ≥8, and de novo mHSPC; both ENZA+ADT groups had more men with these clinical factors. Men who reached undetectable PSA levels had improved clinical outcomes; e.g., delayed radiographic progression and improved OS (Table). Men on ENZA+ADT (n=348 [68.6%]) were almost 4 times more likely to reach undetectable PSA than men on PBO+ADT (n=89 [17.7%]). Predictors of reaching undetectable PSA on ENZA+ADT using multivariate analysis were the absence of de novo disease (M0 vs M1: odds ratio [OR] 4.3; p=0.001) and baseline PSA levels (OR 3.3; p< 0.0001). Men who reached undetectable PSA on ENZA+ADT had more treatment-emergent adverse events (TEAEs) but fewer serious and grade 3–4 TEAEs vs those with detectable PSA levels. Safety across treatment arms was similar to prior findings.

Conclusion:
Men with mHSPC in ARCHES who reached undetectable PSA levels had improved clinical outcomes and less severe AEs. Men were more likely to reach undetectable PSA on ENZA+ADT vs PBO+ADT. The absence of de novo disease and baseline PSA levels may help identify men who reach undetectable PSA on ENZA+ADT.

Table
JL1004E Table

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Funding: Funding for this research was provided by Pfizer, Inc. and Astellas Pharma, Inc.
Acknowledgements: Medical writing and editorial support funded by both sponsor companies was provided by Terrance Ku, MSc, and Jane Beck, MA (Hons), from Complete HealthVizion, and Adam Anazim, BSc, and Julie Stimmel, PhD, from Onyx, a Prime Global agency.