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

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP29-01 RAPID, DURABLE, AND DEEP PROSTATE-SPECIFIC ANTIGEN RESPONSE FOLLOWING ADDITION OF DAROLUTAMIDE TO ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN ARASENS Fred Saad, Bertrand Tombal, Maha Hussain, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Luke T. Nordquist, Ronald Tutrone, Neal D. Shore, Laurence Belkoff, Shivani Kapur, Jay Jhaveri, Jorge Ortiz, Shankar Srinivasan, Frank Verholen, and Matthew R. Smith Fred SaadFred Saad More articles by this author , Bertrand TombalBertrand Tombal More articles by this author , Maha HussainMaha Hussain More articles by this author , Karim FizaziKarim Fizazi More articles by this author , Cora N. SternbergCora N. Sternberg More articles by this author , E. David CrawfordE. David Crawford More articles by this author , Luke T. NordquistLuke T. Nordquist More articles by this author , Ronald TutroneRonald Tutrone More articles by this author , Neal D. ShoreNeal D. Shore More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Shivani KapurShivani Kapur More articles by this author , Jay JhaveriJay Jhaveri More articles by this author , Jorge OrtizJorge Ortiz More articles by this author , Shankar SrinivasanShankar Srinivasan More articles by this author , Frank VerholenFrank Verholen More articles by this author , and Matthew R. SmithMatthew R. Smith More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In ARASENS (NCT02799602), darolutamide (DARO) in combination with androgen-deprivation 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. Source of Funding: This trial was funded by Bayer AG and Orion Corporation. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e380 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fred Saad More articles by this author Bertrand Tombal More articles by this author Maha Hussain More articles by this author Karim Fizazi More articles by this author Cora N. Sternberg More articles by this author E. David Crawford More articles by this author Luke T. Nordquist More articles by this author Ronald Tutrone More articles by this author Neal D. Shore More articles by this author Laurence Belkoff More articles by this author Shivani Kapur More articles by this author Jay Jhaveri More articles by this author Jorge Ortiz More articles by this author Shankar Srinivasan More articles by this author Frank Verholen More articles by this author Matthew R. Smith More articles by this author Expand All Advertisement PDF downloadLoading ...