(UroToday.com) The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 was host to a prostate cancer abstracts poster session. Dr. Fred Saad presented the results of a secondary analysis of ARASENS evaluating PSA outcomes with darolutamide + docetaxel + ADT triplet therapy in patients with high- and low-volume metastatic hormone-sensitive prostate cancer (mHSPC).
ARASENS was an international, phase 3 trial that randomly assigned mHSPC patients in a 1:1 ratio to receive darolutamide (600 mg twice daily) or matching placebo, both in combination with ADT + docetaxel. The addition of darolutamide to ADT + docetaxel was shown to reduce the risk of death by 32.5% (HR: 0.68; 95% CI: 0.57 to 0.80, p<0.0001).1 Results of an ad hoc analysis of ARASENS demonstrated that these overall survival benefits were similar irrespective of disease volume:2
- High volume: HR=0.69, 95% CI: 0.57 – 0.82
- Low volume: HR=0.68, 95% CI: 0.41 – 1.13
This study aims to report PSA outcomes in these volume subgroups. PSA was measured at screening and every 12 weeks thereafter. Study outcomes included the proportion of patients achieving undetectable PSA (<0.2 ng/mL) and time to PSA progression. The associations between undetectable PSA at any time with time to PSA progression and overall survival (OS) were evaluated using Kaplan-Meier estimates with HRs (95% CI) using a stratified Cox regression model.
Of 1,305 patients, 77% and 23% had high and low volume disease, respectively.
Of 1,305 patients, 1,005 (77%) had high volume and 300 (23%) had low volume disease. Rapid undetectable PSA response as early as 12 weeks was achieved in nearly twice as many patients receiving darolutamide versus placebo and continued to increase for both the high and low volume subgroups over time:
- 24 weeks:
- High volume: 43% versus 22% in favor of darolutamide
- Low volume: 67% versus 32%
- 52 weeks:
- High volume: 55% versus 24%
- Low volume: 78% versus 35%
- At any time:
- High volume: 62% versus 26%
- Low volume: 84% versus 38%
Patients receiving darolutamide who achieved undetectable PSA had improved time to PSA progression (high volume subgroup HR: 0.11, 95% CI: 0.07–0.16; low volume subgroup HR: 0.02, 95% CI :0.004–0.10) and improved overall survival (high volume subgroup HR 0.20; 95% CI 0.15–0.27; low volume subgroup HR 0.34; 95% CI 0.14–0.79) versus those who did not.
Time to PSA progression was prolonged in patients receiving darolutamide versus placebo in both the high volume (HR: 0.30; 95% CI: 0.24–0.37) and low volume subgroups (HR: 0.09; 95% CI 0.05–0.18).
Dr. Saad concluded that early treatment intensification with darolutamide + ADT + docetaxel allows patients with high and low volume mHSPC to achieve rapid, deep, and durable PSA responses that are associated with improved time to PSA progression and OS.
Presented by: Fred Saad, MD, FRCS, Professor and Chief of Urology, Director of GU Oncology, University of Montreal Endowed Chair in Prostate Cancer, University of Montreal Hospital Center, Montreal, Quebec
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
References: