MP29-01 RAPID, DURABLE, AND DEEP PROSTATE-SPECIFIC ANTIGEN RESPONSE FOLLOWING ADDITION OF DAROLUTAMIDE TO ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN ARASENS

Abstract

INTRODUCTION AND OBJECTIVE: In ARASENS (NCT02799602), darolutamide (DARO) in combination with androgendeprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI 0.57‐0.80; P<0.0001) vs ADT + docetaxel in patients with metastatic hormone‐sensitive prostate cancer (mHSPC). We report on prostate‐specific antigen (PSA) responses and kinetics data from ARASENS. METHODS: Patients with mHSPC were randomized 1:1 to DARO 600 mg twice daily or placebo (PBO), both with ADT + docetaxel. Serum PSA was measured at screening and every 12 weeks. Analyses included undetectable PSA (<0.2 ng/mL), ≥50% and ≥90% reductions in PSA from baseline (PSA50, PSA90), and times to PSA progression and PSA50/PSA90. Post hoc landmark analyses evaluated the association between undetectable PSA at weeks 24 and 36 with overall survival (OS) and time to PSA progression. RESULTS: For 1305 patients in the full analysis set (DARO, 651; PBO, 654), median (range) PSA levels at study entry were 30.3 (0.0‐9219.0) and 24.2 (0.0‐11,947.0) ng/mL, respectively. Patients in the DARO group demonstrated rapid PSA90 response, with 67.6% achieving PSA90 within 12 weeks, 82.0% within 24 weeks, and 84.9% at any time compared with 42.8%, 54.4%, and 59.0% in the PBO group, respectively (Figure). DARO was associated with deep PSA response, with median PSA at nadir of 0.020 ng/mL vs 0.495 ng/mL for PBO. Undetectable PSA was achieved in more than twice the number of patients receiving DARO vs PBO at 24 weeks (48.7% vs 23.9%), continuing to increase at 36 and 52 weeks with DARO (57.1% and 60.2%). Compared with patients who did not achieve undetectable PSA, patients receiving DARO who achieved undetectable PSA at 24 and 36 weeks had improved OS (HR [95% CI] 0.47 [0.35‐0.63] and 0.37 [0.28‐0.49]) and prolonged time to PSA progression (HR [95% CI] 0.28 [0.18‐0.42] and 0.23 [0.15‐0.34]), showing durable PSA response that was maintained over time. CONCLUSIONS: Patients with mHSPC receiving DARO + ADT + docetaxel achieved rapid, durable, and deep PSA responses, correlating with improved OS and prolonged time to PSA progression vs PBO + ADT + docetaxel.