Clinical use and outcomes of androgen-receptor pathway inhibitors triplet therapy for metastatic hormone-sensitive prostate cancer (ARAAT).
Authors: McKay Rana R. , Morgans Alicia K. , Khan Nasreen , Constantinovici Niculae , Chen Guifang , Ghadessi Mercedeh , Appukkuttan Sreevalsa , Jhaveri Jay , George Daniel J. 
Published: February 2025

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Background:
In the pivotal phase 3 ARASENS trial, patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received darolutamide in combination with androgen-deprivation therapy (ADT) + docetaxel (DOC) had longer overall survival (OS) vs ADT+DOC. Triplet therapy with darolutamide or abiraterone is recommended for high-risk patients with mHSPC; however, data on routine clinical use and outcomes of triplet therapy are lacking.
Methods:
This retrospective cohort analysis used the ConcertAI Patient360 database, a geographically diverse US oncology electronic medical record source. Adult patients with mHSPC who initiated triplet therapy with darolutamide+ADT+DOC (DAR) or abiraterone+ADT+DOC (ABI) from 1/2020–1/2024 were included. Outcomes included the proportion of patients achieving 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 OS. PSA response during index treatment is reported at 6 and 12 months. Kaplan–Meier (K–M) estimated probability for discontinuation and progression to mCRPC are reported at 18 months.
Results:
A total of 243 patients initiated DAR (n=141) and ABI (n=102) for mHSPC. The median age was 66 years; 80% had an Eastern Cooperative Oncology Group performance status score of 0/1; and >80% completed ≥6 DOC cycles. The median baseline PSA was 36 ng/mL for DAR vs 20 ng/mL for ABI. Median follow-up duration was 16 months for the DAR cohort and 19 months for the ABI cohort. More patients in the DAR cohort achieved a PSA response at 6 and 12 months compared with those in the ABI cohort (Table). At 18 months, K–M probability of discontinuation was 25% for DAR vs 38% for ABI, and probability of progression to mCRPC was 24% for DAR vs 46% for ABI (Table). At the end of the follow-up period, 91% of patients in the DAR cohort were alive compared with 78% in the ABI cohort.
Conclusions:
Using a real-world dataset, treatment discontinuation rates, progression to mCRPC, and PSA responses were all favorable in patients with mHSPC receiving triplet therapy with DAR vs ABI. Further investigation is warranted.

Key study outcomes.

Key outcomes
DAR (n=141)
ABI (n=102)

PSA drop ≥90% from baseline

At 6 months*
90 (88.2%)
38 (65.5%)

At 12 months
†

94 (91.3%)
43 (74.1%)

PSA drop to undetectable level (<0.2 ng/mL)

At 6 months*
45 (44.1%)
19 (32.8%)

At 12 months
†

63 (61.2%)
27 (46.6%)

K–M probability of treatment discontinuation at 18 months (95% CI)
0.245 (0.177−0.334)
0.376 (0.286−0.484)

K–M probability of progression to mCRPC at 18 months (95% CI)
0.244 (0.175−0.335)
0.460 (0.358−0.574)

For the PSA response analysis, patients were required to have baseline PSA ≥1 ng/mL and >1 ng/mL PSA test during index treatment. *At 6 months, DAR n=102; ABI n=58.
†
At 12 months, DAR n=103; ABI n=58. CI, confidence interval.