(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13th and 15th 2025, was host to the Poster Session A: Prostate Cancer. Dr. Rana McKay presented Clinical use and outcomes of androgen-receptor pathway inhibitors triplet therapy for metastatic hormone-sensitive prostate cancer (ARAAT).
Dr. McKay began her presentation by discussing the pivotal Phase 3 ARASENS trial. In this study, patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received triplet therapy—darolutamide in combination with androgen deprivation therapy (ADT) and docetaxel—had improved overall survival (32% lower risk of death) compared to those who received ADT and docetaxel alone.1 Moreover, in the PEACE-1 the risk of death was 18% lower in patients who received triplet therapy compared to ADT + Docetaxel alone.2
Based on the results of ARASENS and the PEACE-1 study, triplet therapy with darolutamide or abiraterone is recommended for high-volume patients with mHSPC.1,2 However, real-world data on the routine clinical use of triplet therapy and outcomes remain limited.
This was a retrospective cohort analysis using the ConcertAI Patient360 database, a geographically diverse U.S. oncology electronic medical record source. The investigators identified adult patients with mHSPC who initiated triplet therapy with darolutamide + ADT + docetaxel or abiraterone + ADT + docetaxel between January 2020 and January 2024.
Inclusion and exclusion criteria are summarized below:
The outcomes of interest included the proportion of patients achievi ng a prostate-specific antigen (PSA) response (≥90% decline or undetectable levels <0.2 ng/mL), treatment discontinuation, progression to metastatic castration-resistant prostate cancer (mCRPC), and overall survival. Unadjusted Kaplan–Meier analysis was used to estimate the probability of treatment discontinuation and progression to mCRPC at 18 months.
The investigators identified and included a total of 242 patients who initiated triplet therapy—141 in the darolutamide cohort and 101 in the abiraterone cohort. Patient characteristics are summarized in the table below. Briefly, the median age was 66 years, over 75% had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, and >80% completed at least six cycles of docetaxel. The median baseline PSA was 36 ng/mL in the darolutamide cohort and 22 ng/mL in the abiraterone cohort.
The median follow-up duration was 16 months for the darolutamide group and 19 months for the abiraterone group. More patients in the darolutamide cohort achieved a PSA90 response at 12 months (92% vs. 61%) compared to those in the abiraterone cohort.
Notably, at the end of the follow-up period, 91% of patients in the darolutamide cohort were alive compared with 78% in the abiraterone cohort.
At 18 months, the Kaplan–Meier estimated probability of treatment discontinuation was lower for darolutamide-treated patients (21% vs. 32% for abiraterone) as illustrated below.
Additionally, the probability of progression to mCRPC was 24% for darolutamide versus 46% for abiraterone, as shown below.
Dr. McKay concluded her presentation with the following key messages:
- In this real-world cohort of patients with mHSPC, triplet therapy with darolutamide was associated with lower treatment discontinuation rates, reduced progression to mCRPC, and higher PSA response rates compared to abiraterone.
- The ARAAT real-world study strengthens the evidence supporting the combination of darolutamide with ADT and docetaxel as an effective treatment for mHSPC.
Presented by: Rana McKay, MD, Medical Oncologist, University of California San Diego (UCSD), CA, USA.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
References:
- Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino Á, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Méndez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. doi: 10.1056/NEJMoa2119115. Epub 2022 Feb 17. PMID: 35179323; PMCID: PMC9844551.
- Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Fléchon A, Tombal B, Supiot S, Berthold D, Ronchin P, Kacso G, Gravis G, Calabro F, Berdah JF, Hasbini A, Silva M, Thiery-Vuillemin A, Latorzeff I, Mourey L, Laguerre B, Abadie-Lacourtoisie S, Martin E, El Kouri C, Escande A, Rosello A, Magne N, Schlurmann F, Priou F, Chand-Fouche ME, Freixa SV, Jamaluddin M, Rieger I, Bossi A; PEACE-1 investigators. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695-1707. doi: 10.1016/S0140-6736(22)00367-1. Epub 2022 Apr 8. PMID: 35405085.