PD10-10: Impact of baseline disease volume and prior docetaxel therapy on prostate-specific antigen-related outcomes in patients with metastatic hormone-sensitive prostate cancer treated with enzalutamide plus androgen deprivation therapy

Neal D. Shore, E. David Crawford, Russell Z. Szmulewitz, Daniel Petrylak, Jeffrey Holzbeierlein, Arnauld Villers, Arun Azad, Antonio Alcaraz, Boris Alekseev, Taro Iguchi, Francisco Gomez-Veiga, Brad Rosbrook, Benoit Baron, Gabriel P. Haas, Arnulf Stenzl, Andrew J. Armstrong

Introduction: Enzalutamide (ENZA) + androgen deprivation therapy (ADT) significantly reduced the risk of radiographic progression or death in men with metastatic hormone-sensitive prostate cancer (mHSPC), regardless of baseline prostate-specific antigen (PSA) levels (ARCHES; NCT02677896). Here, we further assess PSA-related outcomes in patients enrolled in ARCHES by disease volume and prior docetaxel therapy at study entry.

Methods: Patients with mHSPC were randomized 1:1 to receive ENZA (160 mg/day) + ADT or placebo (PBO) + ADT. Primary endpoint was radiographic progression-free survival. Secondary endpoints included time to PSA progression and PSA undetectable rate. Post hoc analyses were performed based on disease volume and prior docetaxel at study entry, which were stratification factors, as well as on time to 50% PSA reduction and time to undetectable (<0.2 ng/mL) PSA.

Results: Of the overall population (n=1150), 423 (36.8%) patients had low-volume disease and 205 (17.8%) patients reported prior docetaxel use. ENZA + ADT significantly improved PSA-related outcomes versus PBO + ADT, regardless of disease volume or prior docetaxel use at study entry (Table). The proportion of patients with =50% PSA reduction from baseline ranged from 85–95% for ENZA + ADT and 18–66% for PBO + ADT across the different patient subgroups.

Conclusions: ENZA + ADT provides improvements in all assessed PSA-related outcomes versus PBO + ADT in patients with mHSPC, irrespective of disease volume or prior docetaxel therapy, with the limitation that the true baseline PSA is unknown for some patients due to prior ADT use in this patient population. Source of

Funding: This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide. Medical writing and editorial assistance were provided by Lianne Young, BSc (Hons), and Jane Beck from Complete HealthVizion, funded by the study sponsors.