(UroToday.com) The 2023 AUA annual meeting included an advanced prostate cancer session, featuring a presentation by Dr. Fred Saad discussing rapid, durable and deep PSA response following the addition of darolutamide to ADT and docetaxel in ARASENS. In ARASENS ( NCT02799602), darolutamide in combination with 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).1 Reductions in PSA to undetectable levels (<=0.2 ng/mL) or >=90% decline from baseline have been associated with improved outcomes, including overall survival. At the 2023 AUA annual meeting, Dr. Saad and colleagues reported on PSA responses and kinetics data from ARASENS.
Patients with mHSPC were randomized 1:1 to darolutamide 600 mg twice daily or placebo, 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 and time to PSA progression.
For 1,305 patients in the full analysis set (darolutamide, 651; placebo, 654), median PSA levels at study entry were 30.3 (range: 0.0–9219.0) and 24.2 (range: 0.0–11,947.0) ng/mL, respectively. Patients in the darolutamide 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 placebo group, respectively:
Additionally, as follows is a figure showing the PSA50 responses:
Darolutamide significantly prolonged time to PSA progression versus placebo (HR 0.26, 95% CI 0.21-0.31):
Patients receiving darolutamide who achieved undetectable PSA at 24 and 36 weeks had increased time to PSA progression with risk reductions of 72% (HR 0.28, 95% CI 0.18-0.42) and 77% (HR 0.23, 95% CI 0.15-0.34), respectively, versus those who did not achieve undetectable PSA, showing durable PSA response that was maintained over time:
Darolutamide + ADT + docetaxel was associated with deep PSA response, with a median PSA nadir of 0.020 (IQR 0.02, 0.25) ng/mL versus 0.495 (IQR 0.09, 2.85) ng/mL for placebo + ADT + docetaxel. Undetectable PSA was achieved in more than twice the number of patients receiving darolutamide versus placebo at 24 weeks (48.7% versus 23.9%) and continued to increase at 36 and 52 weeks and at any time:
Among darolutamide-treated patients, achievement of undetectable PSA at 24 and 36 weeks was associated with improved overall survival. Risk reductions of death were 53% (HR 0.47, 95% CI 0.35-0.63) and 63% (HR 0.37, 95% CI 0.28-0.49), respectively, versus those who did not achieve undetectable PSA:
Dr. Saad concluded his presentation discussing rapid, durable and deep PSA response following the addition of darolutamide to ADT and docetaxel in ARASENS with the following take-home messages:
- Patients with mHSPC receiving darolutamide + ADT + docetaxel achieved rapid, durable, and deep PSA responses, correlating with improved overall survival and prolonged time to PSA progression vs placebo + ADT + docetaxel
- These data support using PSA response as a prognostic indicator of clinical outcomes in patients with mHSPC
Presented by: Fred Saad, MD, FRSC, Professor, Department of Surgery, Raymond Garneau Chair in Prostate Cancer, Université de Montréal, Montréal, QC
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023
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